| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ataxia v2.153 | NEU1 |
Bryony Thompson gene: NEU1 was added gene: NEU1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: NEU1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NEU1 were set to 39482827; 38600684; 33516873; 32753397; 32472645 Phenotypes for gene: NEU1 were set to sialidosis type 1, MONDO:0019346 Review for gene: NEU1 was set to GREEN Added comment: NEU1 encodes the lysosomal sialidase Neu1. Biallelic loss‑of‑function variants in NEU1 cause sialidosis type 1, an autosomal recessive lysosomal storage disorder characterised by progressive myoclonic ataxia, myoclonus, seizures and visual impairment. Functional assays in patient‑derived iPSC neurons and HEK293T cells demonstrate reduced Neu1 protein and enzymatic activity, supporting loss‑of‑function as the disease mechanism. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.151 | NAXE |
Bryony Thompson gene: NAXE was added gene: NAXE was added to Ataxia. Sources: Literature Mode of inheritance for gene: NAXE was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NAXE were set to 38419707; 37274027; 36773198; 35637064; 34678889; 34120322; 31745726; 30022751; 27616477 Phenotypes for gene: NAXE were set to encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, MONDO:0020781 Review for gene: NAXE was set to GREEN Added comment: At least 8 families with biallelic loss‑of‑function NAXE variants cause early‑onset progressive encephalopathy with brain edema/leukoencephalopathy and cerebellar ataxia. Functional fibroblast studies show loss of NAXE protein but no rescue experiments; no cis‑regulatory variants are reported. The autosomal recessive inheritance and prominent ataxia make NAXE deficiency (PEBEL1) relevant for the Ataxia gene panel. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.149 | NARS1 |
Bryony Thompson gene: NARS1 was added gene: NARS1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: NARS1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: NARS1 were set to 38495304; 32738225 Phenotypes for gene: NARS1 were set to Neurodevelopmental disorder, MONDO:0700092; neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, MONDO:0100348; neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, MONDO:0030837 Review for gene: NARS1 was set to GREEN Added comment: Both dominant and recessive NARS1‑related neurodevelopmental disorders feature ataxia, aligning them with the Ataxia panel's scope. Manole2020 reports eight unrelated families with de novo heterozygous NARS1 variants causing a dominant neurodevelopmental disorder with microcephaly, seizures and gait ataxia (toxic gain‑of‑function). Beijer2024 describes a de novo in‑frame deletion in a single family causing a dominant neurodevelopmental disorder characterised by cerebellar ataxia, pyramidal signs, developmental delay, intellectual disability and peripheral neuropathy. Manole2020 also identifies thirteen unrelated families with biallelic NARS1 variants resulting in a recessive neurodevelopmental disorder with microcephaly, impaired language and gait ataxia (partial loss‑of‑function). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.148 | TELO2 |
Sangavi Sivagnanasundram gene: TELO2 was added gene: TELO2 was added to Ataxia. Sources: Literature Mode of inheritance for gene: TELO2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TELO2 were set to 36797513 Phenotypes for gene: TELO2 were set to TELO2-related intellectual disability-neurodevelopmental disorder, MONDO:0014848 Review for gene: TELO2 was set to GREEN Added comment: PMID 36797513 reports 13 individuals from 17 families with biallelic TELO2 variants presenting with developmental delay, intellectual disability, microcephaly and ataxia. Ataxia is a prominent feature of this condition. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.147 | TARS2 |
Sangavi Sivagnanasundram gene: TARS2 was added gene: TARS2 was added to Ataxia. Sources: Literature Mode of inheritance for gene: TARS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TARS2 were set to 37454282 Phenotypes for gene: TARS2 were set to combined oxidative phosphorylation defect type 21, MONDO:0014398 Review for gene: TARS2 was set to GREEN Added comment: PMID 37454282 reports at least 5 unrelated families with biallelic TARS2 variants presenting with combined oxidative phosphorylation deficiency type 21, a mitochondrial disorder characterised by developmental delay, intellectual disability, progressive cerebellar ataxia, hypotonia, seizures and elevated lactate. Some of the affected individuals presented with an ataxic gait as well. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.146 | SRPK3 |
Sangavi Sivagnanasundram gene: SRPK3 was added gene: SRPK3 was added to Ataxia. Sources: Literature Mode of inheritance for gene: SRPK3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: SRPK3 were set to 39073169 Phenotypes for gene: SRPK3 were set to intellectual developmental disorder, X-linked 114, MONDO:0975828 Review for gene: SRPK3 was set to AMBER Added comment: PMID 39073169 reports two individuals presenting with intellectual disability, agenesis of the corpus callosum, cerebellar atrophy, abnormal eye movements and progressive ataxia and X-linked variants in SRPK3. One of the variants c.1585G>A:p.Glu529Lys has a FAF of 0.006% in gnomAD v4.1 (96 hets and 32 hemizygotes globally). Supportive knockout zebrafish models recapitulated the ocular and motor phenotype, including evidence of ataxia. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.145 | PIEZO2 |
Sangavi Sivagnanasundram gene: PIEZO2 was added gene: PIEZO2 was added to Ataxia. Sources: Literature Mode of inheritance for gene: PIEZO2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIEZO2 were set to 27974811; 27653382 Phenotypes for gene: PIEZO2 were set to arthrogryposis, distal, with impaired proprioception and touch, MONDO:0014941 Review for gene: PIEZO2 was set to GREEN Added comment: Distal arthrogryposis with impaired proprioception and touch characterised by reduced proprioceptive and tactile sensation, resulting in ataxia, impaired walking, dysmetria, muscle weakness and atrophy, and progressive joint contractures. PMID 27974811 reports 1 individual from a consanguineous family (2nd-degree cousins) with a biallelic stop PIEZO2 variant causing distal arthrogryposis with sensory ataxia, proprioceptive loss, scoliosis and distal muscle weakness PMID 27653382 reports 2 families with compound heterozygous truncating variants (and one missense variant) causing sensory ataxia with proprioceptive loss, progressive scoliosis and congenital joint contractures. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.144 | DYRK1A |
Sangavi Sivagnanasundram gene: DYRK1A was added gene: DYRK1A was added to Ataxia. Sources: Literature Mode of inheritance for gene: DYRK1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DYRK1A were set to 40206408; 25944381 Phenotypes for gene: DYRK1A were set to DYRK1A-related intellectual disability syndrome, MONDO:0013578 Review for gene: DYRK1A was set to GREEN Added comment: DYRK1A syndrome is associated with intellectual disability, speech impairment, autism spectrum disorder, and microcephaly. Affected individuals often share characteristic facial features and may experience feeding difficulties, seizures, hypertonia, walking abnormalities, and foot anomalies. >5 unrelated individuals with monoallelic loss-of-function variants presented with ataxia/ataxic gait abnormalities. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.143 | NALCN |
Bryony Thompson gene: NALCN was added gene: NALCN was added to Ataxia. Sources: Literature Mode of inheritance for gene: NALCN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NALCN were set to 41153398; 37469362; 27633718; 25864427 Phenotypes for gene: NALCN were set to congenital contractures of the limbs and face, hypotonia, and developmental delay, MONDO:0014556 Review for gene: NALCN was set to GREEN Added comment: PMID 25864427, PMID 27633718 and PMID 41153398 report 3 individuals from 3 families with heterozygous de novo missense variants in NALCN causing congenital contractures of the limbs and face, hypotonia, developmental delay and cerebellar ataxia. PMID 37469362 reports 1 proband with mild cerebellar atrophy but no ataxia at the time of assessment. Ataxia can be a feature of the condition. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.141 | MT-TL1 |
Bryony Thompson gene: MT-TL1 was added gene: MT-TL1 was added to Ataxia. Sources: Literature Mode of inheritance for gene gene: MT-TL1 was set to MITOCHONDRIAL Publications for gene: MT-TL1 were set to 40787093; 40707189; 37311680; 36684660; 35869996; 32821290; 32357846; 32357846; 29430542; 28458318 Phenotypes for gene: MT-TL1 were set to MERRF syndrome, MONDO:0010790; Mitochondrial disease, MONDO:0044970 Review for gene: MT-TL1 was set to GREEN Added comment: MELAS syndrome with cerebellar ataxia, stroke‑like episodes and lactic acidosis—Bogdan2022 reports 1 family, PMID 32357846 reports 1 family, PMID 40707189 reports 1 family and PMID 28458318 reports 1 family (total 4 families, 4 independent). MELAS/Kearns–Sayre overlap syndrome with progressive cerebellar ataxia, myoclonus epilepsy and ophthalmoplegia—Yu2018 reports 1 family (1 independent). Adult‑onset cerebellar ataxia with diabetes mellitus and sensorineural hearing loss—Liao2023 reports 2 families (1 independent) carrying the recurrent m.3243A>G variant. Wernicke‑Korsakoff syndrome with gait ataxia, memory loss and thalamic/mammillary lesions—Jimoh2020 reports 1 family (1 independent). MERRF syndrome with myoclonic epilepsy, ataxia, proximal limb weakness, cerebellar atrophy and ragged‑red fibres—Huang2023 reports 1 family (1 independent). Mitochondrial disease with cerebellar ataxia, progressive myopathy, seizures and nephrotic syndrome—Gillespie2025 reports 1 family (1 independent). These mitochondrial disease phenotypes frequently include cerebellar ataxia, aligning with the Ataxia panel's focus on disorders where ataxia is a prominent feature; therefore MT‑TL1 is appropriate for inclusion as a diagnostic‑grade gene on this panel. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.139 | MT-TK |
Bryony Thompson gene: MT-TK was added gene: MT-TK was added to Ataxia. Sources: Literature Mode of inheritance for gene gene: MT-TK was set to MITOCHONDRIAL Publications for gene: MT-TK were set to 34025555; 32538863; 29756269; 26995359; 25559684 Phenotypes for gene: MT-TK were set to MERRF syndrome, MONDO:0010790; Mitochondrial disease, MONDO:0044970 Review for gene: MT-TK was set to GREEN Added comment: Variants in MT‑TK cause mitochondrial disease, most prominently MERRF syndrome, in which cerebellar ataxia is a frequent manifestation, and have also been reported in a rare MELAS/LS overlap presentation. MERRF syndrome (mitochondrial disease with myoclonus, epilepsy, myopathy, cardiac involvement and ataxia) is associated with the heteroplasmic m.8344A>G mt‑tRNA Lys mutation in 26 independent families (56 patients) across Italian, German, Chinese and other cohorts; the phenotype includes cerebellar ataxia in a majority of cases. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.137 | RFC4 |
Sangavi Sivagnanasundram gene: RFC4 was added gene: RFC4 was added to Ataxia. Sources: Literature Mode of inheritance for gene: RFC4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RFC4 were set to 39106866 Phenotypes for gene: RFC4 were set to Morimoto-Ryu-Malicdan neuromuscular syndrome, MONDO:0975848 Review for gene: RFC4 was set to GREEN Added comment: PMID 39106866 reports four individuals from four unrelated families with biallelic RFC4 variants presenting with a multisystemic disorder that includes cerebellar ataxia, incoordination, muscle weakness, hearing impairment and reduced body weight. Two of the affected individuals also presented with gait ataxia. Note: one of the reported variants has a high FAF in gnomAD v4.1 for an AR gene (c.996+2dup - FAF 0.0581%). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.136 | NOTCH2NLC_NIID_GGC |
Bryony Thompson changed review comment from: NM_001364012.2:c.-164GGC[X] Expanded repeat in NOTCH2NLC sequence is (GGC)9(GGA)2(GGC)2. Large number of families and sporadic cases reported with expansions, with a range of neurodegenerative phenotypes, including: dementia, Parkinsonism/tremor, peripheral neuropathy, leukoencephalopathy, myopathy, motor neurone disease. Normal repeat range: 4-40, 1 control had 61 repeats and may have been a presymptomatic carrier. Intermediate range: 41-60 identified in Parkinson's disease Pathogenic repeat range: >=60-520 Mechanism of disease is translation of repeat expansion into a toxic polyglycine protein, identified in both mouse models and tissue samples from affected individuals. Sources: Expert list; to: NM_001364012.2:c.-164GGC[X] Expanded repeat in NOTCH2NLC sequence is (GGC)9(GGA)2(GGC)2. Large number of families and sporadic cases reported with expansions, with a range of neurodegenerative phenotypes, including: dementia, Parkinsonism/tremor, peripheral neuropathy, leukoencephalopathy, myopathy, motor neurone disease, ataxia. Normal repeat range: 4-40, 1 control had 61 repeats and may have been a presymptomatic carrier. Intermediate range: 41-60 identified in Parkinson's disease Pathogenic repeat range: >=60-520 Mechanism of disease is translation of repeat expansion into a toxic polyglycine protein, identified in both mouse models and tissue samples from affected individuals. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.135 | PYCR2 |
Sangavi Sivagnanasundram gene: PYCR2 was added gene: PYCR2 was added to Ataxia. Sources: Literature Mode of inheritance for gene: PYCR2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PYCR2 were set to 27860360; 27130255 Phenotypes for gene: PYCR2 were set to hypomyelinating leukodystrophy 10, MONDO:0014632 Review for gene: PYCR2 was set to GREEN Added comment: PMID 27860360 reports only one individual with homozygous c.577G>A p.Val193Met variants presenting with progressive microcephaly, severe global developmental delay, failure to thrive, hypomyelinating leukodystrophy and an ataxic gait. PMID: 27130255 reports 11 families (10 consanguineous families) with homozygous PYCR2 variants presenting with a range of neurodevelopmental phenotypes including ataxia, failure to thrive, microcephaly, craniofacial dysmorphism, progressive psychomotor disability, hyperkinetic movements, and axial hypotonia with variable appendicular spasticity. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.134 | PTPMT1 |
Sangavi Sivagnanasundram gene: PTPMT1 was added gene: PTPMT1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: PTPMT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTPMT1 were set to 39279645 Phenotypes for gene: PTPMT1 were set to Neurodevelopmental disorder with ataxia and brain abnormalities MONDO:0978300 Review for gene: PTPMT1 was set to GREEN Added comment: Neurodevelopmental disorder with ataxia and brain abnormalities (NEDAXBA) is characterised by developmental delay, microcephaly, facial dysmorphism, epilepsy, spasticity, cerebellar ataxia and nystagmus, sensorineural hearing loss, optic atrophy, and bulbar dysfunction with neonatal/infantile onset. PMID 39279645 reports five individuals from two consanguineous families with biallelic loss-of-function PTPMT1 variants presenting with infantile-onset cerebellar ataxia, developmental delay, microcephaly, epilepsy, sensorineural hearing loss and optic atrophy. Patient fibroblast rescue of mitochondrial fragmentation and a zebrafish ptpmt1 knockout recapitulating mitochondrial dysfunction support pathogenicity. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.133 | POLR2A |
Sangavi Sivagnanasundram gene: POLR2A was added gene: POLR2A was added to Ataxia. Sources: Literature Mode of inheritance for gene: POLR2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POLR2A were set to 33665635 Phenotypes for gene: POLR2A were set to neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities, MONDO:0032829 Review for gene: POLR2A was set to GREEN Added comment: Ataxia isn't a prominent feature in all POLR2A-affected individuals; however, it can be a presenting feature in most individuals. PMID 33665635 reports 7/12 individuals with heterozygous POLR2A variants presenting with a neurodevelopmental disorder featuring ataxia, developmental delay, seizures, hypotonia, joint hypermobility and short stature. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.132 | PIGK |
Sangavi Sivagnanasundram gene: PIGK was added gene: PIGK was added to Ataxia. Sources: Literature Mode of inheritance for gene: PIGK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIGK were set to 32220290 Phenotypes for gene: PIGK were set to neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures, MONDO:0030037 Review for gene: PIGK was set to GREEN Added comment: PMID 32220290 reports 5 of 8 individuals (four independent families) with biallelic PIGK variants presenting with developmental delay/intellectual disability, hypotonia, cerebellar atrophy, cerebellar ataxia, epilepsy and dysmorphic features. Ataxia is a prominent feature of this condition. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.131 | PAK1 |
Sangavi Sivagnanasundram gene: PAK1 was added gene: PAK1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: PAK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PAK1 were set to 30290153 Phenotypes for gene: PAK1 were set to intellectual developmental disorder with macrocephaly, seizures, and speech delay, MONDO:0032568 Mode of pathogenicity for gene: PAK1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: PAK1 was set to GREEN Added comment: PMID 30290153 reports 2 individuals from 2 families with de novo heterozygous PAK1 missense variants presenting with developmental delay, macrocephaly, seizures and ataxic gait. Patient fibroblast assays show gain‑of‑function effects (increased JNK/AKT phosphorylation, reduced dimerisation, enhanced filopodia) that are rescued by the PAK1 inhibitor FRAX486. Ataxia is a prominent feature of this condition. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.129 | OGDHL |
Sangavi Sivagnanasundram gene: OGDHL was added gene: OGDHL was added to Ataxia. Sources: Literature Mode of inheritance for gene: OGDHL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: OGDHL were set to 34800363 Phenotypes for gene: OGDHL were set to Yoon-Bellen neurodevelopmental syndrome, MONDO:0859221 Review for gene: OGDHL was set to GREEN Added comment: Affected individuals with biallelic mutations in OGDHL present with gait ataxia, epilepsy, hearing loss, visual impairment, and developmental delay. 4 of 8 families reported ataxia as a presenting phenotype. Functional studies in Drosophila and human neuronal cells demonstrate loss of OGDHL function. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.127 | NDUFA13 |
Sangavi Sivagnanasundram changed review comment from: PMID 39963288 reports >5 unrelated individuals with biallelic NDUFA13 variants presenting with infantile‑onset neurodevelopmental disorder characterised by cerebellar ataxia, spasticity, hypotonia and epilepsy. Note: One of the reported variants has a higher FAF in gnomAD v4.1 for an AR gene - c.187G>A (Glu63Lys). Sources: Literature; to: PMID 39963288 reports >5 unrelated individuals with biallelic NDUFA13 variants presenting with infantile‑onset neurodevelopmental disorder characterised by cerebellar ataxia, spasticity, hypotonia and epilepsy. Note: One of the reported variants has a higher FAF in gnomAD v4.1 for an AR gene - c.187G>A (Glu63Lys) FAF 0.06%. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.127 | NDUFA13 |
Sangavi Sivagnanasundram gene: NDUFA13 was added gene: NDUFA13 was added to Ataxia. Sources: Literature Mode of inheritance for gene: NDUFA13 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NDUFA13 were set to 39963288 Phenotypes for gene: NDUFA13 were set to mitochondrial complex I deficiency, nuclear type 28, MONDO:0032632 Review for gene: NDUFA13 was set to GREEN Added comment: PMID 39963288 reports >5 unrelated individuals with biallelic NDUFA13 variants presenting with infantile‑onset neurodevelopmental disorder characterised by cerebellar ataxia, spasticity, hypotonia and epilepsy. Note: One of the reported variants has a higher FAF in gnomAD v4.1 for an AR gene - c.187G>A (Glu63Lys). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.126 | MYORG |
Sangavi Sivagnanasundram gene: MYORG was added gene: MYORG was added to Ataxia. Sources: Literature Mode of inheritance for gene: MYORG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MYORG were set to 39180105; 32451491 Phenotypes for gene: MYORG were set to basal ganglia calcification, idiopathic, 7, autosomal recessive, MONDO:0032673 Review for gene: MYORG was set to GREEN Added comment: PMID 32451491 and 39180105 report 5 families with biallelic MYORG variants causing primary familial brain calcification with cerebellar ataxia, pyramidal signs and dysarthria. Ataxia is a prominent feature of this condition. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.125 | MTO1 |
Sangavi Sivagnanasundram gene: MTO1 was added gene: MTO1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: MTO1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MTO1 were set to 29331171 Phenotypes for gene: MTO1 were set to Mitochondrial disease, MONDO:0044970 Review for gene: MTO1 was set to GREEN Added comment: PMID 29331171 reports 7 individuals from 7 families with biallelic MTO1 variants presenting with ataxia, lactic acidosis, developmental delay/intellectual disability, cardiomyopathy and combined oxidative phosphorylation deficiency. The condition is a mitochondrial disorder, and ataxia is a core neurological manifestation. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.124 | EIF2AK2 |
Sangavi Sivagnanasundram gene: EIF2AK2 was added gene: EIF2AK2 was added to Ataxia. Sources: Literature Mode of inheritance for gene: EIF2AK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EIF2AK2 were set to 37284702; 32197074 Phenotypes for gene: EIF2AK2 were set to leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, MONDO:0030035 Review for gene: EIF2AK2 was set to GREEN Added comment: PMID 32197074 reports six individuals with heterozygous missense EIF2AK2 variants presenting with developmental delay, leukoencephalopathy and progressive ataxia (gait or truncal ataxia. PMID 37284702 reports another individual with a de novo heterozygous variant and nystagmus, hypotonia, global developmental delay, ataxia and spasticity. Brain MRI at the age of two revealed diffuse hypomyelination. All the reported missense variants are rare or absent in gnomAD v4. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.123 | CYP7B1 |
Sangavi Sivagnanasundram gene: CYP7B1 was added gene: CYP7B1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: CYP7B1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CYP7B1 were set to 40782215; 29126212 Phenotypes for gene: CYP7B1 were set to hereditary spastic paraplegia 5A, MONDO:0010047 Review for gene: CYP7B1 was set to GREEN Added comment: PMID 29126212 and 40782215 report multiple individuals with autosomal recessive hereditary spastic paraplegia type 5 (SPG5) characterised by progressive spastic gait and gait ataxia. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.122 | CTNNB1 |
Sangavi Sivagnanasundram gene: CTNNB1 was added gene: CTNNB1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: CTNNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CTNNB1 were set to 39935833; 35880249 Phenotypes for gene: CTNNB1 were set to CTNNB1-related neurodevelopmental disorder and/or vitreoretinopathy, MONDO:0100571 Review for gene: CTNNB1 was set to GREEN Added comment: Ataxia is a presenting feature of this GDA. PMID 35880249 reports 1 individual from 1 family and PMID 39935833 reports 2 individuals from 2 families, all with de novo heterozygous CTNNB1 variants presenting with neurodevelopmental disorder with spastic diplegia, visual defects, microcephaly, severe developmental delay and ataxic gait. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.120 | MT-ND5 |
Bryony Thompson gene: MT-ND5 was added gene: MT-ND5 was added to Ataxia. Sources: Literature Mode of inheritance for gene gene: MT-ND5 was set to MITOCHONDRIAL Publications for gene: MT-ND5 were set to 35719398; 34025555; 29506874 Phenotypes for gene: MT-ND5 were set to Leber hereditary optic neuropathy, MONDO:0010788; MELAS syndrome, MONDO:0010789; Mitochondrial disease, MONDO:0044970 Review for gene: MT-ND5 was set to GREEN Added comment: MT-ND5 encodes a subunit of mitochondrial Complex I and pathogenic variants are linked to a spectrum of mitochondrial disorders that can feature cerebellar ataxia, a core phenotype for the Ataxia panel. Ng2018 reports six individuals from five families with a maternally inherited m.13094T>C (p.Val253Ala) variant presenting with progressive cerebellar ataxia; the cohort provides five independent families. Barone2022 describes a single case with the heteroplasmic m.13513G>A (p.D393N) variant causing Leber hereditary optic neuropathy together with adult‑onset nephropathy, sensorineural deafness and cerebellar atrophy. Wei2021 aggregates six individuals from six families harbouring the recurrent m.13513G>A variant with MELAS/Leigh overlap syndrome, where ataxia is a prominent feature of the Leigh component. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.118 | MPZ |
Bryony Thompson gene: MPZ was added gene: MPZ was added to Ataxia. Sources: Literature Mode of inheritance for gene: MPZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MPZ were set to 33960567 Phenotypes for gene: MPZ were set to Charcot-Marie-Tooth disease type 1B, MONDO:0007307 Review for gene: MPZ was set to GREEN Added comment: PMID 33960567 reports 6 individuals from 6 families with heterozygous truncating MPZ variants presenting with adult-onset sensory ataxia, mild weakness and demyelinating neuropathy (CMT1B); four variants arose de novo and the recurrent p.Asp104fs variant was observed in multiple families. MPZ is relevant to the Ataxia panel because sensory ataxia is a core feature of the disorder. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.116 | MLC1 |
Bryony Thompson gene: MLC1 was added gene: MLC1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: MLC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MLC1 were set to 41483250; 35468122; 34918859; 31942423 Phenotypes for gene: MLC1 were set to megalencephalic leukoencephalopathy with subcortical cysts 1, MONDO:0024555 Review for gene: MLC1 was set to GREEN Added comment: Four studies together describe 35 individuals from three independent consanguineous families carrying biallelic loss‑of‑function MLC1 variants (homozygous missense p.Ser93Leu, splice‑site c.768+2T>C, and missense p.Cys85Trp). Segregation is confirmed in the families reported by PMID 34918859 and PMID 31942423; the PMID 35468122 variant is recurrent in a distinct South‑American cohort, satisfying the qualifying‑variant gate. The multicentre Italian cohort (PMID 41483250) adds 27 further patients, confirming the classic macrocephaly, developmental delay, cerebellar ataxia, spasticity and subcortical cysts phenotype. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.114 | MINPP1 |
Bryony Thompson gene: MINPP1 was added gene: MINPP1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: MINPP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MINPP1 were set to 40508022; 33257696; 33168985 Phenotypes for gene: MINPP1 were set to pontocerebellar hypoplasia, MONDO:0020135 Review for gene: MINPP1 was set to GREEN Added comment: PMID 33168985, PMID 33257696, and PMID 40508022 report a total of 18 individuals from 12 families with biallelic loss-of-function MINPP1 variants causing pontocerebellar hypoplasia, a severe neurodevelopmental disorder characterised by cerebellar and pontine hypoplasia, ataxia and profound developmental delay. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.112 | MICU1 |
Bryony Thompson gene: MICU1 was added gene: MICU1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: MICU1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MICU1 were set to 40434710; 38380193; 33969448; 33428302 Phenotypes for gene: MICU1 were set to proximal myopathy with extrapyramidal signs, MONDO:0014300 Review for gene: MICU1 was set to GREEN Added comment: Four families with biallelic loss-of-function MICU1 variants are reported across four studies. Affected individuals present with childhood‑onset proximal muscle weakness, markedly elevated CK, developmental delay and extrapyramidal manifestations including ataxia, matching the phenotype of proximal myopathy with extrapyramidal signs. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.110 | MFSD8 |
Bryony Thompson gene: MFSD8 was added gene: MFSD8 was added to Ataxia. Sources: Literature Mode of inheritance for gene: MFSD8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MFSD8 were set to 41045016; 39108195; 38153683; 37090936; 35216386; 30144815; 27146152 Phenotypes for gene: MFSD8 were set to neuronal ceroid lipofuscinosis 7, MONDO:0012588 Review for gene: MFSD8 was set to GREEN Added comment: PMID 41045016 reports five male patients from four families (one independent founder origin) with adult‑onset isolated cerebellar ataxia due to homozygous MFSD8 p.Ile312Thr; PMID 39108195 adds three unrelated families (including two with the same variant and one compound‑heterozygous) presenting with cerebellar ataxia and macular dystrophy; PMID 38153683 describes two siblings from a consanguineous Egyptian family harbouring a homozygous missense c.638C>A variant and a classic CLN7 phenotype of neurodevelopmental regression, seizures and gait ataxia; PMID 30144815 reports a single Russian patient with a homozygous nonsense c.525T>A variant and early‑onset CLN7 features; PMID 27146152 identifies a homozygous nonsense c.1213C>T variant in a child with early‑onset ataxic gait and cerebellar atrophy; PMID 37090936 presents a case with a homozygous splice‑site c.753A>G variant and cerebellar ataxia, myoclonus and visual loss; and PMID 35216386 reports two Turkish siblings homozygous for a synonymous c.750A>G variant causing exon‑8 skipping and CLN7 with cerebellar ataxia. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.108 | MED27 |
Bryony Thompson gene: MED27 was added gene: MED27 was added to Ataxia. Sources: Literature Mode of inheritance for gene: MED27 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MED27 were set to 41017421; 37517035 Phenotypes for gene: MED27 were set to neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia, MONDO:0859137 Review for gene: MED27 was set to GREEN Added comment: PMID 41017421 and PMID 37517035 together report a neurodevelopmental disorder with spasticity, cataracts, cerebellar hypoplasia/ataxia, intellectual disability and developmental delay caused by biallelic MED27 variants. Across the two studies 57 affected individuals from up to 60 families (38 independent origins after collapsing recurrent variants) are described, with core features of gait ataxia, cataracts, spasticity and cerebellar atrophy. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.106 | MED13L |
Bryony Thompson gene: MED13L was added gene: MED13L was added to Ataxia. Sources: Literature Mode of inheritance for gene: MED13L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MED13L were set to 29511999 Phenotypes for gene: MED13L were set to syndromic intellectual disability, MONDO:0000508 Review for gene: MED13L was set to GREEN Added comment: PMID 29511999 reports 36 individuals from 35 families with heterozygous de novo loss-of-function or missense variants in MED13L, presenting with intellectual disability, severe speech impairment, hypotonia and ataxia (observed in ~34% of cases). The gene acts via haploinsufficiency (loss-of-function) with an autosomal dominant de novo inheritance pattern and no contradictory evidence. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.104 | MBOAT7 |
Bryony Thompson gene: MBOAT7 was added gene: MBOAT7 was added to Ataxia. Sources: Literature Mode of inheritance for gene: MBOAT7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MBOAT7 were set to 30701556 Phenotypes for gene: MBOAT7 were set to complex neurodevelopmental disorder, MONDO:0100038 Review for gene: MBOAT7 was set to GREEN Added comment: PMID 30701556 reports 12 individuals from 7 consanguineous Turkish families (5 independent) with biallelic loss‑of‑function variants in MBOAT7 presenting with global developmental delay, severe speech impairment, intellectual disability, early‑onset epilepsy and a characteristic wide‑based ataxic gait with cerebellar dysgenesis. This neurodevelopmental disorder with prominent ataxia aligns with the Ataxia panel’s scope, as ataxic gait is a core feature of the phenotype. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.102 | MAN2B1 |
Bryony Thompson gene: MAN2B1 was added gene: MAN2B1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: MAN2B1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAN2B1 were set to 35242565; 34486965 Phenotypes for gene: MAN2B1 were set to alpha-mannosidosis, MONDO:0009561 Review for gene: MAN2B1 was set to GREEN Added comment: PMID 35242565 reports 12 individuals from 9 families and PMID 34486965 reports 1 individual from 1 family with autosomal recessive alpha‑mannosidosis presenting with childhood‑onset progressive ataxia, hearing loss, intellectual disability and immune deficiency. In total, 13 patients from 10 families (4 independent) carry biallelic loss‑of‑function MAN2B1 variants, including three families with truncating null alleles and one family with a missense allele (c.1061C>T) with variant‑specific functional validation. The disease is a lysosomal storage disorder with a recognisable multisystem phenotype that includes ataxia, making MAN2B1 relevant to the Ataxia panel. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.100 | MAB21L1 |
Bryony Thompson gene: MAB21L1 was added gene: MAB21L1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: MAB21L1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAB21L1 were set to 30487245 Phenotypes for gene: MAB21L1 were set to cerebellar, ocular, craniofacial, and genital syndrome, MONDO:0032774 Review for gene: MAB21L1 was set to GREEN Added comment: PMID 30487245 reports 10 individuals from 5 families with biallelic loss-of-function variants in MAB21L1 presenting with Cerebello-Oculo-Facio-Genital (COFG) syndrome, characterised by cerebellar hypoplasia with ataxia, ocular anomalies, distinctive facial features and genital anomalies. This gene is relevant to the Ataxia panel because the syndrome includes cerebellar hypoplasia and ataxia, core features of the panel's scope. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.98 | LYST |
Bryony Thompson gene: LYST was added gene: LYST was added to Ataxia. Sources: Literature Mode of inheritance for gene: LYST was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LYST were set to 34483340; 28193763; 26944273; 26307451 Phenotypes for gene: LYST were set to Chediak-Higashi syndrome, MONDO:0008963 Review for gene: LYST was set to GREEN Added comment: Multiple studies report that biallelic loss‑of‑function variants in LYST cause Chediak‑Higashi syndrome, a Mendelian lysosomal trafficking disorder that frequently includes cerebellar ataxia. PMID 34483340 describes four families (two independent) with spastic paraplegia, cerebellar ataxia and intellectual disability; PMID 26307451 reports a single adult‑onset family of three siblings with ataxia, parkinsonism and spastic paraparesis; PMID 26944273 (and the overlapping PMID 28193763 cohort) document nine patients from seven families (six independent) with childhood‑onset cerebellar ataxia and progressive neurodegeneration. Across the literature 12 families (9 independent) harbour qualifying biallelic truncating or nonsense LYST variants. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.96 | LRSAM1 |
Bryony Thompson gene: LRSAM1 was added gene: LRSAM1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: LRSAM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: LRSAM1 were set to 30996334 Phenotypes for gene: LRSAM1 were set to Charcot-Marie-Tooth disease axonal type 2P, MONDO:0013753 Review for gene: LRSAM1 was set to GREEN Added comment: PMID 30996334 reports 72 individuals from 8 families (5 independent) with heterozygous in‑frame LRSAM1 variants presenting with adult‑onset sensory ataxia, neuropathic pain and length‑dependent sensory loss. This dominant‑negative mechanism causes Charcot‑Marie‑Tooth disease type 2P, an ataxic neuropathy that falls within the Ataxia panel’s scope of disorders featuring prominent ataxia. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.94 | L2HGDH |
Bryony Thompson gene: L2HGDH was added gene: L2HGDH was added to Ataxia. Sources: Literature Mode of inheritance for gene: L2HGDH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: L2HGDH were set to 42205672; 40870031; 40660807; 38716347; 37275239; 36462087; 33061758 Phenotypes for gene: L2HGDH were set to L-2-hydroxyglutaric aciduria, MONDO:0009370 Review for gene: L2HGDH was set to GREEN Added comment: PMID 36462087, PMID 37275239, PMID 33061758, PMID 40660807, PMID 38716347, PMID 40870031 and PMID 42205672 together report 52 individuals from 38 families with biallelic L2HGDH loss‑of‑function variants presenting with L‑2‑hydroxyglutaric aciduria, characterised by progressive cerebellar ataxia, developmental delay, seizures and movement disorders. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.92 | KIF5A |
Bryony Thompson gene: KIF5A was added gene: KIF5A was added to Ataxia. Sources: Literature Mode of inheritance for gene: KIF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KIF5A were set to 40518753; 31286494; 30778698; 30480035; 29892902 Phenotypes for gene: KIF5A were set to hereditary spastic paraplegia 10, MONDO:0011408 Review for gene: KIF5A was set to GREEN Added comment: Four papers report 12 affected individuals from 4 independent families with heterozygous KIF5A variants (missense and splice) presenting with hereditary spastic paraplegia and cerebellar ataxia; this phenotype includes prominent ataxia and aligns with the Ataxia panel’s scope of disorders where ataxia is a core feature. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.90 | KIF1A |
Bryony Thompson gene: KIF1A was added gene: KIF1A was added to Ataxia. Sources: Literature Mode of inheritance for gene: KIF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KIF1A were set to 38785164; 38681507; 36305856; 36233161; 35326432; 30778698; 27146152 Phenotypes for gene: KIF1A were set to Neurodevelopmental disorder, MONDO:0700092 Review for gene: KIF1A was set to GREEN Added comment: KIF1A is associated with a dominant neurodevelopmental disorder characterised by early‑onset progressive ataxia, cerebellar atrophy, spasticity, hypotonia, seizures, optic nerve atrophy and cognitive impairment. Across 191 reported families (190 independent qualifying families) de novo heterozygous missense variants have been documented with ataxia. A single recessive case with biallelic KIF1A variants and a similar phenotype has also been described but does not meet the family‑count threshold for Green classification. The dominant KIF1A‑associated ataxia phenotype aligns with the Ataxia panel’s scope of disorders where ataxia is a prominent feature. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.88 | KIAA0586 |
Bryony Thompson gene: KIAA0586 was added gene: KIAA0586 was added to Ataxia. Sources: Literature Mode of inheritance for gene: KIAA0586 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIAA0586 were set to 40448720; 39898050; 37131188; 36635699; 32381069; 30120217; 26386247; 26386044; 26026149 Phenotypes for gene: KIAA0586 were set to Joubert syndrome 23, MONDO:0014664 Review for gene: KIAA0586 was set to GREEN Added comment: Across nine studies, 33 families (32 independent) with 37 affected individuals have been reported harbouring biallelic loss‑of‑function KIAA0586 variants. All families present the core Joubert syndrome phenotype – cerebellar vermis hypoplasia, molar‑tooth sign, ataxia, developmental delay and hypotonia – with variable additional features such as chronic airway disease, thoracic dysplasia, ocular‑motor apraxia, epilepsy or SUDEP. Autosomal recessive inheritance is consistently demonstrated (e.g., PMID 26026149 box 30, PMID 26386247 box 31). Functional assays show absent KIAA0586 protein or shortened cilia in patient fibroblasts, but no rescue experiments or orthogonal animal models (e.g., PMID 26026149 box 114; PMID 26386247 box 28). A recurrent frameshift allele (c.428delG) is common (gnomAD AF ≈ 0.003) and observed homozygously in healthy individuals, yet is interpreted as a hypomorphic variant that contributes to disease when paired with a second loss‑of‑function allele. No convincing contradictory evidence has been published. The phenotype’s hallmark ataxia makes KIAA0586 a clear fit for the Ataxia panel, which prioritises genes causing disorders where ataxia is a prominent feature. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.86 | KCTD7 |
Bryony Thompson gene: KCTD7 was added gene: KCTD7 was added to Ataxia. Sources: Literature Mode of inheritance for gene: KCTD7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KCTD7 were set to 38231304; 27742667 Phenotypes for gene: KCTD7 were set to progressive myoclonic epilepsy type 3, MONDO:0012721 Review for gene: KCTD7 was set to GREEN Added comment: PMID 27742667 reports 2 individuals from 1 family with a homozygous frameshift KCTD7 variant presenting with early‑onset progressive myoclonic epilepsy, severe ataxia and neuroregression; functional assays show loss of K⁺ conductance and impaired glutamine transport. PMID 38231304 adds 42 individuals from 36 families (30 independent) with biallelic KCTD7 loss‑of‑function variants (including recurrent missense alleles) who exhibit drug‑resistant seizures, myoclonus, neuroregression and ataxia. The combined evidence of 31 independent families with ataxia. This association aligns with the Ataxia panel’s scope because ataxia is a core, frequently reported feature of KCTD7‑related progressive myoclonic epilepsy. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.84 | KCNMA1 |
Bryony Thompson gene: KCNMA1 was added gene: KCNMA1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: KCNMA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNMA1 were set to 35730691; 35156297; 33178487; 32132200; 31152168 Phenotypes for gene: KCNMA1 were set to Liang-Wang syndrome, MONDO:0032886; Neurodevelopmental disorder, MONDO:0700092 Review for gene: KCNMA1 was set to GREEN Added comment: Liang‑Wang syndrome (loss‑of‑function KCNMA1) is a monoallelic disorder characterised by developmental delay, cognitive impairment, progressive ataxia and movement abnormalities. Across four studies, 12 independent families with de novo LoF variants have been reported (PMID 32132200, PMID 31152168, PMID 35156297, PMID 33178487). A second, recessive loss‑of‑function neurodevelopmental disorder with ataxia has been described in a single compound‑heterozygous family (PMID 31152168); while supportive, it does not meet the family‑count threshold for a diagnostic‑grade rating. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.82 | KCNC1 |
Bryony Thompson gene: KCNC1 was added gene: KCNC1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: KCNC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNC1 were set to 42347804; 40765656; 37203213; 34733949; 32972906; 31353862; 28380698; 27629860 Phenotypes for gene: KCNC1 were set to complex neurodevelopmental disorder, MONDO:0100038; progressive myoclonic epilepsy type 7, MONDO:0014521 Review for gene: KCNC1 was set to GREEN Added comment: Both progressive myoclonic epilepsy with ataxia (MEAK/EPM7) and milder epilepsy with ataxia phenotypes are associated with KCNC1 variants. PMID 28380698, PMID 27629860, PMID 40765656, PMID 32972906 and PMID 34733949 report 31 families (39 patients) with dominant‑negative loss‑of‑function KCNC1 variants causing progressive myoclonus epilepsy, seizures and cerebellar ataxia, fulfilling diagnostic criteria. PMID 31353862, PMID 42347804 and PMID 37203213 describe 6 families (6 patients) with de novo missense KCNC1 variants leading to epilepsy, mild developmental delay and non‑progressive ataxia, also meeting diagnostic criteria. Ataxia is a core feature of both disease spectrums, making KCNC1 a suitable gene for the Ataxia panel. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.80 | KATNIP |
Bryony Thompson gene: KATNIP was added gene: KATNIP was added to Ataxia. Sources: Literature Mode of inheritance for gene: KATNIP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KATNIP were set to 40621737; 32164589; 32164589; 30982090; 30982090; 27245168; 27245168; 26714646; 26714646 Phenotypes for gene: KATNIP were set to Joubert syndrome, MONDO:0018772 Review for gene: KATNIP was set to GREEN Added comment: Seven families (11 affected individuals) with Joubert syndrome, a neurodevelopmental ciliopathy featuring ataxia, hypotonia, developmental delay and cerebellar vermis hypoplasia, harbour homozygous loss‑of‑function KATNIP variants (c.2674C>T (p.Q892*), c.4420del, c.222_232del, c.3756dupC, R1253Qfs*, M1474Cfs*). Zebrafish morpholino knockdown rescued by wild‑type mRNA provides functional validation, and mouse knockout phenotypes support the loss‑of‑function mechanism. Recessive inheritance is well documented across independent families. Joubert syndrome includes prominent ataxia, making KATNIP relevant to the Ataxia panel. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.78 | KARS1 |
Bryony Thompson gene: KARS1 was added gene: KARS1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: KARS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KARS1 were set to 34172899; 31192300; 31192300 Phenotypes for gene: KARS1 were set to leukoencephalopathy, progressive, infantile-onset, with or without deafness, MONDO:0030893 Review for gene: KARS1 was set to GREEN Added comment: PMID 34172899 reports 22 individuals from 16 families and PMID 31192300 reports 5 individuals from 4 families with biallelic KARS1 loss-of-function variants causing early-onset leukoencephalopathy with cerebellar ataxia. Segregation is confirmed in multiple pedigrees, and functional studies—including zebrafish knockout rescue and aminoacyl‑tRNA synthetase activity assays—support a loss‑of‑function mechanism. In total 27 patients from 20 independent families with ataxia. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.76 | JAM2 |
Bryony Thompson gene: JAM2 was added gene: JAM2 was added to Ataxia. Sources: Literature Mode of inheritance for gene: JAM2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: JAM2 were set to 32142645 Phenotypes for gene: JAM2 were set to basal ganglia calcification, idiopathic, 8, autosomal recessive, MONDO:0032938 Review for gene: JAM2 was set to GREEN Added comment: PMID 32142645 reports 7 individuals from 4 families with biallelic loss-of-function JAM2 variants presenting with primary familial brain calcification and cerebellar ataxia. The cerebellar ataxia aligns JAM2 with the Ataxia panel, which captures disorders where ataxia is a prominent feature. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.74 | IQSEC2 |
Bryony Thompson gene: IQSEC2 was added gene: IQSEC2 was added to Ataxia. Sources: Literature Mode of inheritance for gene: IQSEC2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: IQSEC2 were set to 30666632 Phenotypes for gene: IQSEC2 were set to intellectual disability, X-linked 1, MONDO:0010656 Review for gene: IQSEC2 was set to GREEN Added comment: PMID 30666632 reports 7/9 individuals with X‑linked IQSEC2 variants, including de novo loss‑of‑function frameshift and nonsense mutations, with features of gait ataxia. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.72 | INPP4A |
Bryony Thompson gene: INPP4A was added gene: INPP4A was added to Ataxia. Sources: Literature Mode of inheritance for gene: INPP4A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: INPP4A were set to 39315527 Phenotypes for gene: INPP4A were set to Neurodevelopmental disorder, MONDO:0700092 Review for gene: INPP4A was set to GREEN Added comment: PMID 39315527 reports 21 affected individuals from 12 families (9 independent) with biallelic loss‑of‑function INPP4A variants causing a neurodevelopmental disorder characterised by global developmental delay, severe intellectual disability, microcephaly, limb weakness, cerebellar signs and prominent ataxia. Multiple unrelated families (≥3) harbour qualifying LoF variants, and mouse knockout models recapitulate the phenotype. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.70 | HSPD1 |
Bryony Thompson gene: HSPD1 was added gene: HSPD1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: HSPD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HSPD1 were set to 39500555 Phenotypes for gene: HSPD1 were set to hypomyelinating leukodystrophy 4, MONDO:0012824 Review for gene: HSPD1 was set to GREEN Added comment: PMID 39500555 reports 8 individuals with heterozygous de novo missense HSPD1 variants (p.Ala536Pro, p.Ala536Val) presenting with early‑onset hypomyelinating leukodystrophy characterised by nystagmus, tremor, hypotonia, spasticity, ataxia and neuroregression. The dominant‑negative mechanism impairs HSP60 oligomerisation. Ataxia is a core feature, aligning this gene with the Ataxia panel. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.68 | HSD17B4 |
Bryony Thompson gene: HSD17B4 was added gene: HSD17B4 was added to Ataxia. Sources: Literature Mode of inheritance for gene: HSD17B4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HSD17B4 were set to 42231982; 41367148; 40102401; 39379670; 38249302; 32042923; 28830375; 27790638; 27528516 Phenotypes for gene: HSD17B4 were set to Perrault syndrome 1, MONDO:0009300; d-bifunctional protein deficiency, MONDO:0009855 Review for gene: HSD17B4 was set to GREEN Added comment: Both d‑bifunctional protein deficiency and Perrault syndrome caused by biallelic HSD17B4 variants present with cerebellar ataxia, making HSD17B4 relevant to the Ataxia panel. PMID 41367148, PMID 40102401, PMID 27790638, PMID 32042923 and PMID 42231982 together report 11 families (10 independent) with loss‑of‑function HSD17B4 variants causing d‑bifunctional protein deficiency, featuring early‑ to adult‑onset cerebellar ataxia, hearing loss and sometimes seizures or hypergonadotropic hypogonadism. Functional studies in patient fibroblasts, mouse knock‑out models and cilia‑rescue experiments support pathogenicity. Additionally, three families (PMID 27528516, PMID 38249302, PMID 28830375) report Perrault syndrome with ataxia, hearing loss and ovarian dysgenesis (or male infertility). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.66 | GRN |
Bryony Thompson gene: GRN was added gene: GRN was added to Ataxia. Sources: Literature Mode of inheritance for gene: GRN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GRN were set to 39812704; 39394881; 31855245 Phenotypes for gene: GRN were set to neuronal ceroid lipofuscinosis 11, MONDO:0013866 Review for gene: GRN was set to GREEN Added comment: PMID 39812704 reports 1 individual from 1 family with a homozygous frameshift GRN variant presenting with cerebellar ataxia, cone‑rod dystrophy, seizures and cognitive decline. PMID 39394881 describes 9 individuals from 9 unrelated families, all with biallelic loss‑of‑function GRN variants and a core cerebellar ataxia phenotype; seven families share the recurrent frameshift c.768_769dup. PMID 31855245 adds 3 individuals from 2 families carrying distinct homozygous loss‑of‑function GRN variants (c.1A>T and c.709‑3C>G) with early‑onset ataxia, seizures and retinitis pigmentosa. In total these studies comprise 13 patients from 12 families, representing five independent biallelic loss‑of‑function GRN variant origins that cause neuronal ceroid lipofuscinosis 11 (CLN11) with cerebellar ataxia. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.64 | GLS |
Bryony Thompson gene: GLS was added gene: GLS was added to Ataxia. Sources: Literature Mode of inheritance for gene: GLS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GLS were set to 38877099; 38260514; 35913761; 30970188 Phenotypes for gene: GLS were set to glutaminase deficiency, MONDO:0600001 Review for gene: GLS was set to GREEN Added comment: PMID 30970188 reports three families and PMID 35913761 reports two families (total five families, six patients) with biallelic GLS loss‑of‑function variants (5'UTR repeat expansions, frameshift, nonsense or missense coding changes) causing early‑onset developmental delay, progressive cerebellar ataxia and markedly elevated plasma glutamine. Functional studies show ~4‑fold reduced GLS mRNA in patient iPSCs, markedly decreased enzyme activity in patient fibroblasts, and zebrafish glsa knockdown recapitulating neurodevelopmental defects, though rescue experiments are lacking. These findings align with the Ataxia panel because progressive ataxia is a core feature of the panel’s scope of neurological disorders with ataxia. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.61 | GBA1 |
Bryony Thompson gene: GBA1 was added gene: GBA1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: GBA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GBA1 were set to 28736718; 28736718; 28003644; 28003644 Phenotypes for gene: GBA1 were set to Gaucher disease type III, MONDO:0009267 Review for gene: GBA1 was set to GREEN Added comment: PMID 28736718 reports four individuals from four families with biallelic GBA1 missense variants (p.L444P or p.D409H) presenting with neuronopathic Gaucher disease type III, characterised by cerebellar ataxia, ophthalmoplegia and seizures. PMID 28003644 describes five individuals from four families homozygous for p.L444P with the same phenotype, confirming segregation in consanguineous families and excluding a shared founder haplotype. Combined, nine patients from eight independent families carry qualifying GBA1 variants, establishing GBA1‑related type III Gaucher disease as an autosomal recessive loss‑of‑function disorder with high penetrance. Cerebellar ataxia is a prominent feature, making GBA1 a relevant gene for the Ataxia panel, which curates genes causing ataxia phenotypes. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.59 | GAN |
Bryony Thompson gene: GAN was added gene: GAN was added to Ataxia. Sources: Literature Mode of inheritance for gene: GAN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GAN were set to 39602023; 38011432; 36866531; 34114613; 32999401; 31655922; 30532362; 30246730 Phenotypes for gene: GAN were set to giant axonal neuropathy 1, MONDO:0009749 Review for gene: GAN was set to GREEN Added comment: Across eight studies, GAN is associated with 66 patients from nine independent families harbouring biallelic loss‑of‑function variants, presenting with childhood‑onset gait ataxia, peripheral neuropathy, curly/kinky hair, cerebellar ataxia and multisystem neuro‑degeneration. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.57 | GALC |
Bryony Thompson gene: GALC was added gene: GALC was added to Ataxia. Sources: Literature Mode of inheritance for gene: GALC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GALC were set to 36341094; 35002157; 32484059; 26915362 Phenotypes for gene: GALC were set to Krabbe disease, MONDO:0009499 Review for gene: GALC was set to GREEN Added comment: PMID 26915362 reports five affected individuals from a French‑Canadian family with adult‑onset Krabbe disease and predominant cerebellar ataxia; PMID 32484059 describes a single juvenile‑onset case presenting with ataxia, motor regression and rapid disease progression; PMID 35002157 presents two unrelated Indian families with infantile and juvenile Krabbe disease, both showing ataxia, spastic quadriparesis and optic atrophy; PMID 36341094 reports an adult case with gait ataxia, progressive myoclonic epilepsy and an asymmetric occipital lesion. All cases are caused by biallelic loss‑of‑function GALC variants, establishing recessive Krabbe disease as a monogenic disorder with cerebellar ataxia. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.55 | GABRB2 |
Bryony Thompson gene: GABRB2 was added gene: GABRB2 was added to Ataxia. Sources: Literature Mode of inheritance for gene: GABRB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GABRB2 were set to 33325057; 29100083 Phenotypes for gene: GABRB2 were set to complex neurodevelopmental disorder, MONDO:0100038 Review for gene: GABRB2 was set to GREEN Added comment: PMID 33325057 reports 25 individuals from 22 families with heterozygous de novo missense GABRB2 variants presenting with a neurodevelopmental disorder that includes epilepsy, developmental delay and ataxia. Ataxia is observed in three individuals from three independent families. An additional case with ataxia is reported in PMID 29100083. Ataxia is present in >10% of cases, aligning with the Ataxia panel’s focus on disorders where ataxia is a prominent feature. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.53 | FAM149B1 |
Bryony Thompson gene: FAM149B1 was added gene: FAM149B1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: FAM149B1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAM149B1 were set to 34828254; 30905400 Phenotypes for gene: FAM149B1 were set to Joubert syndrome 36, MONDO:0032902 Review for gene: FAM149B1 was set to GREEN Added comment: PMID 30905400 and PMID 34828254 report a total of eight individuals from five families with biallelic loss‑of‑function FAM149B1 variants causing Joubert syndrome 36, a ciliopathy characterised by cerebellar ataxia, oculomotor apraxia, the molar‑tooth sign and, in some cases, oral‑facial‑digital anomalies. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.51 | ERCC6 |
Bryony Thompson gene: ERCC6 was added gene: ERCC6 was added to Ataxia. Sources: Literature Mode of inheritance for gene: ERCC6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERCC6 were set to 38674442; 37532514 Phenotypes for gene: ERCC6 were set to Cockayne syndrome type 2, MONDO:0019570 Review for gene: ERCC6 was set to GREEN Added comment: PMID 37532514 reports 2 individuals from 1 family with biallelic ERRC6 missense variants causing adult‑onset cerebellar ataxia within Cockayne syndrome type B; PMID 38674442 reports 8 individuals from 8 families with biallelic loss‑of‑function ERCC6 variants causing Cockayne syndrome types I‑III with progressive ataxia, spasticity and microcephaly. Combined evidence (9 families reported, 5 independent qualifying families) supports ERCC6 as a diagnostic‑grade gene for the Ataxia panel given the autosomal recessive, highly penetrant loss‑of‑function mechanism and lack of contradictory data. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.49 | DNM1L |
Bryony Thompson gene: DNM1L was added gene: DNM1L was added to Ataxia. Sources: Literature Mode of inheritance for gene: DNM1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DNM1L were set to 41244260; 38481935; 36212643; 33718295; 31868880 Phenotypes for gene: DNM1L were set to encephalopathy due to mitochondrial and peroxisomal fission defect, MONDO:0054865 Review for gene: DNM1L was set to GREEN Added comment: Four papers (PMID 38481935, PMID 31868880, PMID 36212643, PMID 33718295) each report a single family with a heterozygous DNM1L missense variant and ataxia; PMID 41244260 aggregates 14 additional families with ataxia among a cohort of 66 DNM1L families, including six de novo missense variants and the recurrent p.Arg403Cys hotspot. In total 18 families (17 independent families with qualifying de novo or recurrent variants) demonstrate an autosomal dominant, dominant‑negative loss‑of‑function mechanism. Cellular assays show mitochondrial hyperfusion and loss of DRP1 protein, and mouse knockout and Drosophila models confirm impaired mitochondrial fission, although rescue experiments are lacking. This gene is relevant to the Ataxia panel because DNM1L‑related disease presents with progressive ataxia as a core feature within the neurology and neurodevelopmental disorder group. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.47 | COASY |
Bryony Thompson gene: COASY was added gene: COASY was added to Ataxia. Sources: Literature Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COASY were set to 38750253; 36877387; 28489334 Phenotypes for gene: COASY were set to neurodegeneration with brain iron accumulation 6, MONDO:0014290 Review for gene: COASY was set to GREEN Added comment: PMID 38750253 reports 5 individuals from 4 families (3 independent qualifying families) with biallelic COASY loss‑of‑function variants; PMID 28489334 reports 2 siblings from 1 family with compound heterozygous missense variants; PMID 36877387 reports 1 individual from 1 family with a compound heterozygous nonsense‑missense genotype. All cases present with early‑onset neurodegeneration often including ataxia, epilepsy, developmental delay and cerebellar atrophy or brain iron accumulation. COASY‑associated neurodegeneration frequently manifests with childhood‑onset ataxia and cerebellar involvement, making it directly relevant to the Ataxia panel which targets disorders where ataxia is a core feature. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.45 | CLN8 |
Bryony Thompson gene: CLN8 was added gene: CLN8 was added to Ataxia. Sources: Literature Mode of inheritance for gene: CLN8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CLN8 were set to 36011304; 31982899; 30741402 Phenotypes for gene: CLN8 were set to neuronal ceroid lipofuscinosis 8, MONDO:0010830 Review for gene: CLN8 was set to GREEN Added comment: PMID 31982899, PMID 30741402 and PMID 36011304 report a total of 6 patients from 4 unrelated families with biallelic CLN8 variants causing neuronal ceroid lipofuscinosis 8, a neurodegenerative disorder characterised by seizures, progressive ataxia, visual loss and neuroregression; the presence of progressive ataxia makes this association relevant to the Ataxia panel. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.43 | CEP120 |
Bryony Thompson gene: CEP120 was added gene: CEP120 was added to Ataxia. Sources: Literature Mode of inheritance for gene: CEP120 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CEP120 were set to 38050708; 27208211 Phenotypes for gene: CEP120 were set to Joubert syndrome 31, MONDO:0033310 Review for gene: CEP120 was set to GREEN Added comment: PMID 38050708 and PMID 27208211 together report seven individuals from five families with biallelic CEP120 variants causing Joubert syndrome 31, characterised by cerebellar vermis hypoplasia, molar tooth sign, ataxic gait and abnormal breathing; ataxia is a core feature aligning this gene with the Ataxia panel. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.41 | CEP104 |
Bryony Thompson gene: CEP104 was added gene: CEP104 was added to Ataxia. Sources: Literature Mode of inheritance for gene: CEP104 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CEP104 were set to 41965849; 35359234; 31625690; 26477546 Phenotypes for gene: CEP104 were set to Joubert syndrome 25, MONDO:0014770; ciliopathy, MONDO:0005308 Review for gene: CEP104 was set to GREEN Added comment: CEP104 encodes a centrosomal tip protein involved in ciliary assembly. Biallelic loss‑of‑function variants in CEP104 are linked to two distinct phenotypes that feature ataxia, fitting the Ataxia panel’s scope. Luo2019, PMID 26477546 and PMID 41965849 together report five unrelated families (five probands) with Joubert syndrome, a ciliopathy characterised by cerebellar vermis hypoplasia, molar tooth sign, developmental delay, hypotonia and ataxia, caused by compound heterozygous or homozygous loss‑of‑function CEP104 variants. Badv2022 describes a consanguineous family with a homozygous nonsense CEP104 variant in a child presenting with mild intellectual disability, hypotonia and gait ataxia but normal brain MRI, representing a distinct neurodevelopmental disorder. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.39 | CACNA1C |
Bryony Thompson gene: CACNA1C was added gene: CACNA1C was added to Ataxia. Sources: Literature Mode of inheritance for gene: CACNA1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CACNA1C were set to 34163037; 31291898 Phenotypes for gene: CACNA1C were set to Neurodevelopmental disorder, MONDO:0700092 Review for gene: CACNA1C was set to GREEN Added comment: CACNA1C encodes the α1C subunit of the L-type voltage‑dependent calcium channel (Cav1.2). PMID 34163037 reports 22 families with heterozygous CACNA1C variants causing a neurodevelopmental disorder that includes ataxia, developmental delay/intellectual disability, autism, epilepsy and hypotonia. PMID 31291898 describes a single family with an intronic CACNA1C variant co‑segregating with autosomal dominant cerebellar ataxia. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.37 | B4GALNT1 |
Bryony Thompson gene: B4GALNT1 was added gene: B4GALNT1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: B4GALNT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: B4GALNT1 were set to 40171946; 39145292; 37510308; 35775650 Phenotypes for gene: B4GALNT1 were set to hereditary spastic paraplegia 26, MONDO:0012213 Review for gene: B4GALNT1 was set to GREEN Added comment: PMID 35775650 reports 1 individual from 1 family, PMID 40171946 reports 2 individuals from 1 family, PMID 39145292 reports 1 individual from 1 family, and PMID 37510308 reports 5 individuals from 1 family, all carrying biallelic loss‑of‑function variants in B4GALNT1. Affected individuals present with early‑onset hereditary spastic paraplegia, progressive spastic gait, cerebellar ataxia, dystonia, optic atrophy, hearing loss and intellectual disability. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.35 | ARV1 |
Bryony Thompson gene: ARV1 was added gene: ARV1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: ARV1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARV1 were set to 37749428; 32165008 Phenotypes for gene: ARV1 were set to developmental and epileptic encephalopathy, 38, MONDO:0014868 Review for gene: ARV1 was set to GREEN Added comment: PMID 37749428 reports 1 family and 5 other families identified by a literature review, and PMID 32165008 reports 2 families (3 families total) with autosomal recessive ARV1 loss-of-function variants causing early infantile epileptic encephalopathy 38, characterised by seizures, developmental delay, progressive cerebellar ataxia (often with elevated α‑fetoprotein) Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.33 | ANK3 |
Bryony Thompson gene: ANK3 was added gene: ANK3 was added to Ataxia. Sources: Literature Mode of inheritance for gene: ANK3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ANK3 were set to 40879451; 36777705 Phenotypes for gene: ANK3 were set to Neurodevelopmental disorder, MONDO:0700092 Review for gene: ANK3 was set to GREEN Added comment: ANK3 encodes ankyrin‑G, a neuronal scaffold protein, and pathogenic variants have been linked to neurodevelopmental disorders featuring cerebellar ataxia. Maroofian2025 reports five individuals from three unrelated consanguineous families with biallelic loss‑of‑function ANK3 variants (splice and frameshift) presenting with childhood‑onset cerebellar ataxia, developmental delay, intellectual disability, hypotonia and variable epilepsy. The disorder follows autosomal recessive inheritance, shows high penetrance, and mouse knockout recapitulates the ataxic phenotype, supporting loss‑of‑function as the mechanism. Younus2023 describes a single Pakistani consanguineous family with a homozygous missense ANK3 p.Tyr60His variant; the proband has intellectual disability, ataxia, seizures, speech impairment and aggressive behaviour. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.31 | AIFM1 |
Bryony Thompson gene: AIFM1 was added gene: AIFM1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: AIFM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: AIFM1 were set to 39601015; 37603145; 32337346; 31523922; 31188924; 28842795; 25934856 Phenotypes for gene: AIFM1 were set to Charcot-Marie-Tooth disease X-linked recessive 4, MONDO:0010689; X-linked hereditary sensory and autonomic neuropathy with hearing loss, MONDO:0010378; severe X-linked mitochondrial encephalomyopathy, MONDO:0010437; spondyloepimetaphyseal dysplasia, Bieganski type, MONDO:0010275 Review for gene: AIFM1 was set to GREEN Added comment: AIFM1 encodes a mitochondrial flavoprotein required for NADH oxidation and caspase‑independent apoptosis. Pathogenic variants cause a spectrum of X‑linked neuro‑developmental and mitochondrial disorders that frequently feature cerebellar ataxia. **X‑linked hypomyelination with spondylometaphyseal dysplasia (H‑SMD)** – six unrelated families (12 patients) with loss‑of‑function AIFM1 variants present with hypomyelination, spondylometaphyseal dysplasia, ataxia and additional neurologic signs (PMID 28842795). **Severe X‑linked mitochondrial encephalomyopathy** – two families (two patients) with loss‑of‑function missense variants display cerebellar ataxia, peripheral neuropathy, hearing loss, optic atrophy and muscle weakness (PMID 37603145; PMID 25934856). **X‑linked hereditary sensory and autonomic neuropathy with hearing loss** – three independent families (12 patients) harbor distinct missense AIFM1 variants and share cerebellar ataxia, peripheral neuropathy, sensorineural hearing loss and colour‑vision deficiency (PMID 31523922; PMID 32337346; PMID 39601015). ** Charcot-Marie-Tooth disease X‑linked recessive 4** – one family (four patients) with a gain‑of‑function missense variant shows hearing loss, peripheral neuropathy, distal muscle wasting and ataxic gait (PMID 31188924). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.29 | AARS2 |
Bryony Thompson gene: AARS2 was added gene: AARS2 was added to Ataxia. Sources: Literature Mode of inheritance for gene: AARS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AARS2 were set to 39853526; 38507676; 35084689; 31705293; 31347571; 31099476; 30706699; 29666464; 28322004 Phenotypes for gene: AARS2 were set to Mitochondrial disease, MONDO:0044970; ovarioleukodystrophy, MONDO:0020506 Review for gene: AARS2 was set to GREEN Added comment: PMID 31099476, PMID 30706699, PMID 29666464, PMID 35084689 and PMID 31347571 together report seven families (five independent qualifying families) with biallelic loss‑of‑function AARS2 variants causing adult‑onset leukoencephalopathy, cerebellar atrophy and progressive ataxia. PMID 31705293 describes a single family with recessive cerebellar ataxia without leukoencephalopathy. PMID 39853526, PMID 28322004 and PMID 38507676 report eight families (two independent qualifying families) with ovarioleukodystrophy (leukoencephalopathy + ovarian failure). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.28 | CLP1 |
Sangavi Sivagnanasundram gene: CLP1 was added gene: CLP1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: CLP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CLP1 were set to 38622473; 34584079 Phenotypes for gene: CLP1 were set to pontocerebellar hypoplasia type 10, MONDO:0014349 Review for gene: CLP1 was set to AMBER Added comment: PMID 38622473 reports 14 of 15 Turkish individuals with reported pontocerebellar hypoplasia and ataxia as a presenting phenotype however they all carry the same homozygous variant - c.419G>A p.Arg140His - FAF 0.002% in gnomAD v4.1. The authors speculate that this is a founder variant in the Turkish population. PMID 34584079 describes functional assays conducted on patient fibroblast cell lines that show a loss-of-function effect compared to the WT. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.27 | ATG12 |
Sangavi Sivagnanasundram gene: ATG12 was added gene: ATG12 was added to Ataxia. Sources: Literature Mode of inheritance for gene: ATG12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATG12 were set to 41895291 Phenotypes for gene: ATG12 were set to ATG12-related neurodevelopmental disorder, MONDO:0700092 Review for gene: ATG12 was set to AMBER Added comment: PMID 41895291 reports two individuals (both from unrelated consanguineous families) with biallelic ATG12 variants presenting with congenital ataxia, developmental delay, intellectual disability, hypotonia, seizures and cerebellar vermis hypoplasia. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.25 | C19orf12 |
Sangavi Sivagnanasundram gene: C19orf12 was added gene: C19orf12 was added to Ataxia. Sources: Literature Mode of inheritance for gene: C19orf12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C19orf12 were set to 39755877 Phenotypes for gene: C19orf12 were set to neurodegeneration with brain iron accumulation 4, MONDO:0013674 Review for gene: C19orf12 was set to GREEN Added comment: Mitochondrial membrane protein-associated neurodegeneration (MPAN)/NBIA 4 is a rare neurodegenerative disorder characterised by spastic paraplegia, parkinsonism, and psychiatric and/or behavioural symptoms. PMID 39755877 reports 4 individuals from 4 unrelated families with rare homozygous variants in C19orf12, with ataxia as a presenting feature. Note, C19orf12 was formally known as SPG43 Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.22 | ASL |
Sangavi Sivagnanasundram gene: ASL was added gene: ASL was added to Ataxia. Sources: Literature Mode of inheritance for gene: ASL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ASL were set to 38044746 Phenotypes for gene: ASL were set to argininosuccinic aciduria, MONDO:0008815 Review for gene: ASL was set to AMBER Added comment: PMID 38044746 reports 7 unrelated individuals with argininosuccinic aciduria and ataxia as a presenting feature however only two of the individuals were reported to have genetic testing. Both individuals presented with compound heterozygous variants that are present in gnomAD v4.1 but rare enough for AR association. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.19 | ACOX1 |
Sangavi Sivagnanasundram gene: ACOX1 was added gene: ACOX1 was added to Ataxia. Sources: Literature Mode of inheritance for gene: ACOX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ACOX1 were set to 38923841; 37846133 Phenotypes for gene: ACOX1 were set to Mitchell syndrome, MONDO:0030073 Review for gene: ACOX1 was set to AMBER Added comment: Three unrelated individuals presenting with Mitchell syndrome, characterised by progressive gait ataxia, sensorineural hearing loss, visual impairment, ichthyosis and polyneuropathy. They all carry the same heterozygous missense variant c.710A>G, p.Asn237Ser, which is absent in gnomAD v4.1. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.18 | ALG6 |
Sangavi Sivagnanasundram gene: ALG6 was added gene: ALG6 was added to Ataxia. Sources: Literature Mode of inheritance for gene: ALG6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ALG6 were set to 27287710 Phenotypes for gene: ALG6 were set to ALG6-congenital disorder of glycosylation 1C, MONDO:0011291 Review for gene: ALG6 was set to GREEN Added comment: Multiple individuals reported with ataxia as a presenting phenotype. Note: two of the reported variants have a high FAF for an AR gene c.257+5G>A - FAF 0.1133% in gnomAD v4.1 c.391T>C p.Tyr131His - FAF 3.787% in gnomAD v4.1. This is a known polymorphism in ALG6. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.15 | ABCA2 |
Sangavi Sivagnanasundram gene: ABCA2 was added gene: ABCA2 was added to Ataxia. Sources: Literature Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ABCA2 were set to 38228874 Phenotypes for gene: ABCA2 were set to intellectual developmental disorder with poor growth and with or without seizures or ataxia, MONDO:0032930 Review for gene: ABCA2 was set to GREEN Added comment: Biallelic ABCA2 variants present with a neurological disorder characterised by global developmental delay apparent from infancy, hypotonia, and poor overall growth, sometimes with borderline microcephaly. 3 unrelated individuals reported with ataxia as a presenting feature. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.14 | ATL2 |
chirag patel gene: ATL2 was added gene: ATL2 was added to Ataxia. Sources: Other Mode of inheritance for gene: ATL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: ATL2 were set to Cerebellar ataxia, MONDO:0000437, ATL2-related Mode of pathogenicity for gene: ATL2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: ATL2 was set to RED Added comment: ESHG 2026 7 living individuals from 1 large multigeneration family presenting with early onset (<20yrs but slowly progressive) ataxia, dysarthria, and cerebellar atrophy. WGS (SR and LR) identified a rare heterozygous 2-bp deletion variant in the ATL2 gene. The variant is deeply intronic in the canonical transcript but leads to a frameshift in an alternate transcript (ATL2-2, NM_001330461.2:c.1208_1209del, p.(Arg403Thrfs*6)), which is predominantly expressed in the brain and cerebellum. The same variant seen in 2 other unrelated families with dominant cerebellar ataxia. The variant is positioned in the last exon of this transcript, and it is not expected to cause nonsense-mediated decay but likely leads to a protein with an altered C-terminus. Functional analyses were conducted in ATL2/3 double knockout Cos7 cells with different ATL2 isoforms being reintroduced and subsequent measurements of GTPase activity and confocal imaging. These suggested a gain-of-function effect with increased GTPase activity and altered endoplasmatic reticulum morphology. The proposed disease mechanism is a transcript-specific heterozygous gain-of-function. Sources: Other |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.0 | MME | Gene migrated from ENSG00000196549 to ENSG00000196549 (gene set migration) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.190 | TDP1 | Zornitza Stark edited their review of gene: TDP1: Added comment: Additional family reported in PMID 39576382 with different homozygous missense, c.1432C>T (p.His478Tyr). The affected individual had severe hypotonia, ataxia, distal axonal neuropathy, seizures at 9‑10 months, kyphoscoliosis, hearing/vision loss and moderate cognitive impairment. No other supportive data.; Changed publications: 31182267, 12244316, 39576382 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.186 | ATP2B3 | Bryony Thompson Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.182 | UNC13A |
Zornitza Stark changed review comment from: PMID 41125872 reports 48 individuals with neurodevelopmental disorders and UNC13A variants. Of these, 20 classified as pathogenic. Of these 6 individuals had biallelic variants and presented with severe-to-profound GDD or intellectual disability, hypotonia and seizures of different types (largely controllable with medication) or death in early childhood caused by respiratory failure after pneumonia in one case. Mechanism for this subgroup is LoF with carrier parents unaffected. A second group of 13 patients (21 months to 32 years old) harboured pathogenic, heterozygous de novo missense variants with multiple substitutions at amino acids 808, 811 and 814 (hinge region). They presented with variable degrees of GDD, hypotonia, seizures of different types (mainly refractory to treatment) and typically exhibited ataxia, tremor or dyskinetic movements rarely observed in other patients. Also a family identified with at least four affected members across two generations (4 years to 35 years old) harbouring a pathogenic heterozygous missense variant (C587F) that caused learning difficulties to mild–moderate intellectual disability as well as controlled seizures. Three different types of mechanism of pathogenicity proposed.; to: PMID 41125872 reports 13 patients (21 months to 32 years old) with pathogenic, heterozygous de novo missense variants with multiple substitutions at amino acids 808, 811 and 814 (hinge region). They presented with variable degrees of GDD, hypotonia, seizures of different types (mainly refractory to treatment) and typically exhibited ataxia, tremor or dyskinetic movements rarely observed in other patients. GoF proposed. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.182 | UNC13A | Zornitza Stark Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.174 | CLCN2 |
Zornitza Stark changed review comment from: Association with hyperaldosteronism: Familial hyperaldosteronism type II is an autosomal dominant disorder characterized by hypertension due to increased aldosterone, often with hypokalemia. Patients usually present before age 20 years, although some may present in infancy. The disorder shows incomplete penetrance and variable expressivity; some patients may have normal blood pressure but have an increased aldosterone:renin ratio (ARR) on laboratory testing. At least 6 unrelated families reported. Note bi-allelic variants cause a different phenotype. Association with leukodystrophy: At least six families reported, three with adult onset and three with childhood onset.; to: Association with leukodystrophy is the one relevant to this panel: At least six families reported, three with adult onset and three with childhood onset. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.160 | THG1L | Zornitza Stark edited their review of gene: THG1L: Added comment: LIMITED by ClinGen. Founder variant.; Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.136 | CACNA1A_SCA6_CAG |
Bryony Thompson STR: CACNA1A_SCA6_CAG was added STR: CACNA1A_SCA6_CAG was added to Ataxia. Sources: Expert List Mode of inheritance for STR: CACNA1A_SCA6_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: CACNA1A_SCA6_CAG were set to 20301319; 29325606 Phenotypes for STR: CACNA1A_SCA6_CAG were set to Spinocerebellar ataxia 6 MIM#183086; Episodic ataxia, type 2 MIM#108500 Review for STR: CACNA1A_SCA6_CAG was set to GREEN STR: CACNA1A_SCA6_CAG was marked as clinically relevant STR: CACNA1A_SCA6_CAG was marked as current diagnostic Added comment: NM_023035.2:c.6929_6931CAG[X] PolyQ expansion alters gene binding, impairs transcription factor function, and is toxic to cells expressing the α1ACT – effects consistent with a loss of function Normal: ≤18 repeats Questionable significance: 19 CAG repeats Full penetrance: ≥20 repeats Sources: Expert List |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.134 | BEAN1_SCA31_TGGAA |
Bryony Thompson STR: BEAN1_SCA31_TGGAA was added STR: BEAN1_SCA31_TGGAA was added to Ataxia. Sources: Expert List Mode of inheritance for STR: BEAN1_SCA31_TGGAA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: BEAN1_SCA31_TGGAA were set to 19878914; 31755042 Phenotypes for STR: BEAN1_SCA31_TGGAA were set to Spinocerebellar ataxia 31 MIM#117210 Review for STR: BEAN1_SCA31_TGGAA was set to GREEN STR: BEAN1_SCA31_TGGAA was marked as clinically relevant STR: BEAN1_SCA31_TGGAA was marked as current diagnostic Added comment: Complex repeat insertion (TGGAA)n, (TAGAA)n, (TAAAA)n, (TAAAATAGAA)n, TGGAA is present only in affected cases. Sequencing showed that the insertion consisted of a preceding TCAC sequence, and 3 pentanucleotide repeat components (TGGAA)n, (TAGAA)n, and (TAAAA)n in all patients tested. 2.5-3.8 KB insertion is associated with disease and RNA toxicity expected to be mechanism of disease Normal and pathogenic cut-offs are based on animal model experiments (PMID: 31755042) Sources: Expert List |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.132 | ATXN8OS_SCA8_CTG |
Bryony Thompson STR: ATXN8OS_SCA8_CTG was added STR: ATXN8OS_SCA8_CTG was added to Ataxia. Sources: Expert List Mode of inheritance for STR: ATXN8OS_SCA8_CTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: ATXN8OS_SCA8_CTG were set to 20301445 Phenotypes for STR: ATXN8OS_SCA8_CTG were set to Spinocerebellar ataxia 8 MIM#608768 Review for STR: ATXN8OS_SCA8_CTG was set to GREEN STR: ATXN8OS_SCA8_CTG was marked as clinically relevant STR: ATXN8OS_SCA8_CTG was marked as current diagnostic Added comment: NR_002717.2:n.1073CTA[X]1103CTG[X] ATXN8 (CAG)n(TAG)n vs ATXN8OS on opposite strand (CTA)n(CTG)n Both toxic RNA and toxic protein gain of function mechanisms likely contribute to disease mechanism Normal alleles: 15-50 combined (CTA·TAG)n(CTG·CAG)n repeats Alleles of questionable significance: 50-70 repeats. Reduced penetrance allele size: found for (CTA·TAG)n(CTG·CAG)n repeats of all sizes Higher penetrance allele size: ≥80 (CTA·TAG)n(CTG·CAG)n repeats most often seen in individuals with ataxia; however, repeat sizes ranging from 71 to more than 1300 repeats have been found both in individuals who develop ataxia and in those who do not. Sources: Expert List |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.130 | ATXN7_SCA7_CAG |
Bryony Thompson STR: ATXN7_SCA7_CAG was added STR: ATXN7_SCA7_CAG was added to Ataxia. Sources: Expert List Mode of inheritance for STR: ATXN7_SCA7_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: ATXN7_SCA7_CAG were set to 29325606; 20301433 Phenotypes for STR: ATXN7_SCA7_CAG were set to Spinocerebellar ataxia 7 MIM#164500 Review for STR: ATXN7_SCA7_CAG was set to GREEN STR: ATXN7_SCA7_CAG was marked as clinically relevant STR: ATXN7_SCA7_CAG was marked as current diagnostic Added comment: NM_000333.3:c.89_91AGC[X] Gain of function mechanism of disease Normal: ≤27 repeats Mutable normal: 28-33 repeats, meiotically unstable, but not associated with an abnormal phenotype. Pathogenic reduced penetrance: 34-36 repeats, when manifestations occur, they are more likely to be later onset and milder than average Pathogenic full penetrance: 37-460 repeats Sources: Expert List |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.128 | ATXN3_SCA3_CAG |
Bryony Thompson STR: ATXN3_SCA3_CAG was added STR: ATXN3_SCA3_CAG was added to Ataxia. Sources: Expert List Mode of inheritance for STR: ATXN3_SCA3_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: ATXN3_SCA3_CAG were set to 20301375; 29325606 Phenotypes for STR: ATXN3_SCA3_CAG were set to Machado-Joseph disease MIM#109150; Spinocerebellar ataxia type 3 Review for STR: ATXN3_SCA3_CAG was set to GREEN STR: ATXN3_SCA3_CAG was marked as clinically relevant STR: ATXN3_SCA3_CAG was marked as current diagnostic Added comment: NM_004993.5:c.886_888CAG[X] Toxic aggregation and mislocalization in neurons is mechanism of disease Normal: ≤44 repeats, mostly <31 repeats Intermediate: 45-59 repeats, some intermediate alleles are not associated with classic clinical features of SCA3 Pathogenic (full penetrance): ≥60 repeats Sources: Expert List |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.126 | ATXN1_SCA1_CAG |
Bryony Thompson STR: ATXN1_SCA1_CAG was added STR: ATXN1_SCA1_CAG was added to Ataxia. Sources: Expert List Mode of inheritance for STR: ATXN1_SCA1_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: ATXN1_SCA1_CAG were set to 29325606; 20301363 Phenotypes for STR: ATXN1_SCA1_CAG were set to Spinocerebellar ataxia 1 MIM#164400 Review for STR: ATXN1_SCA1_CAG was set to GREEN STR: ATXN1_SCA1_CAG was marked as clinically relevant STR: ATXN1_SCA1_CAG was marked as current diagnostic Added comment: NM_000332.3:c.589_591CAG[X] Toxic protein aggregation is mechanism of disease Normal: ≤35 CAG repeats or 36-44 CAG repeats with CAT interruptions Mutable normal (intermediate): 36-38 CAG repeats without CAT interruptions Full-penetrance: ≥39 CAG repeats without CAT interruptions or ≥46 uninterrupted CAG repeats with CAT interruptions and additional CAGs Sources: Expert List |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.124 | ATXN10_SCA10_ATTCT |
Bryony Thompson STR: ATXN10_SCA10_ATTCT was added STR: ATXN10_SCA10_ATTCT was added to Ataxia. Sources: Expert List Mode of inheritance for STR: ATXN10_SCA10_ATTCT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: ATXN10_SCA10_ATTCT were set to 20301354 Phenotypes for STR: ATXN10_SCA10_ATTCT were set to Spinocerebellar ataxia 10 MIM#603516 Review for STR: ATXN10_SCA10_ATTCT was set to GREEN STR: ATXN10_SCA10_ATTCT was marked as clinically relevant STR: ATXN10_SCA10_ATTCT was marked as current diagnostic Added comment: NM_013236.2:c.1430+54822ATTCT[X] Toxic RNA gain-of-function mechanism of disease Normal alleles: 10-32 ATTCT repeats Alleles of questionable significance: 33-280 ATTCT repeats Reduced-penetrance alleles: 33-850 repeats Full-penetrance alleles: 800-4,500 ATTCT repeats Sources: Expert List |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.122 | ATN1_DRPLA_CAG |
Bryony Thompson STR: ATN1_DRPLA_CAG was added STR: ATN1_DRPLA_CAG was added to Ataxia. Sources: Expert List Mode of inheritance for STR: ATN1_DRPLA_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: ATN1_DRPLA_CAG were set to 29325606; 20301664 Phenotypes for STR: ATN1_DRPLA_CAG were set to Dentatorubral-pallidoluysian atrophy MIM#125370 Review for STR: ATN1_DRPLA_CAG was set to GREEN STR: ATN1_DRPLA_CAG was marked as clinically relevant STR: ATN1_DRPLA_CAG was marked as current diagnostic Added comment: NM_001007026.1:c.1462_1464CAG[X] Toxic gain of function mechanism of disease Benign: ≤35 repeats Mutable normal: 20-35 repeats Pathogenic: ≥48 repeats Age <20 years: ≥63 repeats - ataxia, myoclonus, seizures, progressive intellectual deterioration Age 21-40 years 61-69 repeats, >40 years 48-67 repeats: ataxia, choreoathetosis, dementia, psychiatric disturbance Sources: Expert list Sources: Expert List |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.100 | PLD3 | Bryony Thompson edited their review of gene: PLD3: Added comment: Another rare missense c.77T>C p.Ile26Thr was identified in a SCA case. Now, 2 reported variants are associated with SCA.; Changed publications: 29053796, 30312375, 30312384, 38059248 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.96 | Bryony Thompson Copied gene MME from panel Ataxia - adult onset | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.96 | MME |
Bryony Thompson gene: MME was added gene: MME was added to Ataxia. Sources: Expert Review Green,Royal Melbourne Hospital,GeneReviews,Expert Review Red,Victorian Clinical Genetics Services Mode of inheritance for gene: MME was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MME were set to 27583304 Phenotypes for gene: MME were set to ?Spinocerebellar ataxia type 43, 617018 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.63 | PIK3R5 | chirag patel commented on gene: PIK3R5: ClinGen DISPUTED - Apr 2025 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.53 | SKOR2 |
Bryony Thompson gene: SKOR2 was added gene: SKOR2 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: SKOR2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SKOR2 were set to 40890458; 29997391; 21937600 Phenotypes for gene: SKOR2 were set to complex neurodevelopmental disorder with motor features MONDO:0100516 Review for gene: SKOR2 was set to GREEN Added comment: 3 unrelated families with consistent phenotypes and a supportive mouse model: PMID: 40890458 - 2 unrelated consanguineous Iranian families with a combination of learning disability, facial dysmorphisms, and motor and speech impairments with homozygous variants (c.374 G>C: p.Arg125Pro & c.1271_1274del: p.K424Rfs*71). The homozygous missense variant segregated with disease in 8 individuals (no unaffected individuals tested were homozygous). PMID: 29997391 - proband with neurodevelopmental delay, hypotonia, ataxia, cerebellar dysplasia from a consanguineous Turkish family with a homozygous null variant (NM_001278063.1:c.2750C>G; p.Ser917*). None of the 4 healthy siblings were homozygous for the variant. PMID: 21937600 - Skor2 -/- mouse model had defective Purkinje cell development, a severe reduction of granule cell proliferation and a malformed cerebellum. Mouse had unstable gait. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.49 | PRDX3 | Zornitza Stark Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.47 | ATXN2_SCA2_CAG |
Bryony Thompson STR: ATXN2_SCA2_CAG was added STR: ATXN2_SCA2_CAG was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for STR: ATXN2_SCA2_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: ATXN2_SCA2_CAG were set to 40741828 Phenotypes for STR: ATXN2_SCA2_CAG were set to Spinocerebellar ataxia type 2 MONDO:0008458 Review for STR: ATXN2_SCA2_CAG was set to GREEN STR: ATXN2_SCA2_CAG was marked as clinically relevant STR: ATXN2_SCA2_CAG was marked as current diagnostic Added comment: Cohort of paediatric-onset SCA2 cases. The infantile onset group (n=9) had expansions ≥88 repeats, and the juvenile onset group (n=13) had expansions ≥43 repeats. Paediatric SCA2 phenotype includes developmental delay and seizures (infantile-onset) and cerebellar degeneration similar to adults in the juvenile group. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.44 | CSNK2B |
Boris Keren gene: CSNK2B was added gene: CSNK2B was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: CSNK2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CSNK2B were set to PMID: 34041744 Phenotypes for gene: CSNK2B were set to intellectual disability; ataxia; epilepsy Penetrance for gene: CSNK2B were set to Complete Review for gene: CSNK2B was set to GREEN Added comment: PMID: 34041744. 25 patients with mostly de novo LoF or missenses and NDD. 25% have ataxia Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.42 | PDE1B |
Zornitza Stark gene: PDE1B was added gene: PDE1B was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: PDE1B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDE1B were set to 40492975 Phenotypes for gene: PDE1B were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PDE1B-related Review for gene: PDE1B was set to GREEN Added comment: PMID:40492975 reported seven individuals from five unrelated families identified with biallelic PDE1B variants. Three truncating (p.Gln45Ter, p.Gln86Ter, p.Ser298Alafs*6) and three splicing variants (c.594 + 2 T>G, c.735 + 5G>A, c.837-1G>C) were identified from these patients in total. They presented with an early-onset movement disorder characterised by hypotonia in infancy, progressing to ataxia and dystonia in early childhood, with motor and speech delay, and intellectual disability. Functional evidence is also available for these variants. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.40 | ELFN1 |
Krithika Murali gene: ELFN1 was added gene: ELFN1 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: ELFN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ELFN1 were set to PMID:40576023 Phenotypes for gene: ELFN1 were set to Neurodevelopmental disorder, MONDO:0700092, ELFN1-related Review for gene: ELFN1 was set to GREEN Added comment: PMID: 40576023 report 8 individuals from 5 unrelated families and 6 previously reported patients from 2 families. Most patients had homozygous biallelic deletions / PTCs in ELFN1 (including one involving 5'UTR). One family had biallelic missense variants, All patients had dev delay/ID. Other features included autism/ADHD/behavioural issues, hypotonia/muscle weakness, paediatric-onset ataxia/movement disorder and epilepsy. Supportive functional modelling in mice and zebrafish. Some emerging evidence for haploinsufficiency. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.38 | SIDT2 |
Sarah Milton gene: SIDT2 was added gene: SIDT2 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: SIDT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SIDT2 were set to PMID: 40541391 Phenotypes for gene: SIDT2 were set to Lysosomal storage disease, MONDO:0002561, SIDT2-related Review for gene: SIDT2 was set to AMBER Added comment: Encodes a lysosomal membrane protein involved in trafficking of RNA into the lysosome for degradation via RNAutophagy. 1 affected individual described in PMID: 40541391 with two variants in SIDT2 presenting with progressive neurological decline in childhood with poor coordination, dysarthria, ataxia, cerebellar atrophy and cognitive decline. One variant confirmed to be maternally inherited, the other inheritance was unknown due to lack of availability of family members (as such phase not confirmed). Variants were c.1586G>A (?listed as p.Arg529Trp however protein consequence should be p.Arg529Gln) and c.2032C>T|p.Arg678Trp. Functional studies of patient fibroblasts showed markers of autophagy impairment and mouse models with reduced expression of SIDT2 had signs of progressive incoordination. LOF proposed mechanism. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.35 | RAB3A |
Bryony Thompson gene: RAB3A was added gene: RAB3A was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: RAB3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RAB3A were set to 40166812 Phenotypes for gene: RAB3A were set to autosomal dominant cerebellar ataxia MONDO:0020380 Review for gene: RAB3A was set to GREEN Added comment: 18 individuals from 10 unrelated cerebellar ataxia families were heterozygous for a RAB3A missense variant. 9/10 families had a recurrent variant - p.Arg83Trp. The age of onset of the ataxia was adult, except for 3 paediatric/adolescent onset cases. Additionally, 4 individuals from 3 families (F11, F12, F13) with 2 de novo missense and a stopgain had similar phenotypes consisting of a neurodevelopmental syndrome with progressive cognitive deficits and spasticity. F14 was a singleton with a missense variant and HMSN & optic atrophy. Initially included in the cohort for gait ataxia, was found to be a sensory ataxia. There were supporting in vitro functional assays and Drosophila rescue models that suggest partial loss of function as the disease mechanism, but were unable to differentiate the genotype-phenotype correlation for the cerebellar ataxia phenotype vs the neurodevelopmental syndrome. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.34 | PCNA |
Sangavi Sivagnanasundram gene: PCNA was added gene: PCNA was added to Ataxia - paediatric. Sources: ClinGen Mode of inheritance for gene: PCNA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PCNA were set to 24911150, 33426167, 36990216 Phenotypes for gene: PCNA were set to hereditary ataxia MONDO:0100309 Review for gene: PCNA was set to AMBER Added comment: Classified as Limited by Cerebellar Ataxia GCEP on 09/04/2025 - https://search.clinicalgenome.org/CCID:008778 Two missense variants have been reported across 5 families. Both the missense variants are present in gnomAD (rare enough for AR gene). Method of pathogenicity is still unknown. Affected individuals reported with ataxia, photosensitivity, telangiectasias, and some degree of intellectual disability. Sources: ClinGen |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.32 | SPTAN1 |
Bryony Thompson gene: SPTAN1 was added gene: SPTAN1 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: SPTAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPTAN1 were set to 36331550 Phenotypes for gene: SPTAN1 were set to Spastic paraplegia 91, autosomal dominant, with or without cerebellar ataxia MONDO:0957813 Mode of pathogenicity for gene: SPTAN1 was set to Other Review for gene: SPTAN1 was set to GREEN gene: SPTAN1 was marked as current diagnostic Added comment: 15/31 individuals from 26 unrelated families carrying heterozygous variants in SPTAN1 manifested ataxia, usually with HSP. There were 2 patients with pure ataxia. Suggested that the mechanism of disease for these heterozygous variants was suspected to be dominant negative. Variable age of onset from paediatric to adult onset. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.30 | CAPRIN1 |
Shekeeb S gene: CAPRIN1 was added gene: CAPRIN1 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: CAPRIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CAPRIN1 were set to 39878554 Phenotypes for gene: CAPRIN1 were set to Childhood Dementia; Myoclonus-Ataxia; Sensorimotor Neuropathy; cerebellar atrophy; cortical atrophy Penetrance for gene: CAPRIN1 were set to unknown Review for gene: CAPRIN1 was set to GREEN gene: CAPRIN1 was marked as current diagnostic Added comment: Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.29 | EEFSEC |
Zornitza Stark gene: EEFSEC was added gene: EEFSEC was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: EEFSEC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EEFSEC were set to 39753114 Phenotypes for gene: EEFSEC were set to Neurodevelopmental disorder, MONDO:0700092, EEFSEC-related Review for gene: EEFSEC was set to GREEN Added comment: Nine individuals from 8 unrelated families reported with bi-allelic variants in this gene and progressive neurodevelopmental disorder manifesting with global developmental delay, progressive spasticity, ataxia, and seizures. Cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy. In line with the clinical phenotype, an eEFSec-RNAi Drosophila model displays progressive impairment of motor function, which is reflected in the synaptic defects in this model organisms. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.25 | FDXR |
Zornitza Stark gene: FDXR was added gene: FDXR was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: FDXR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FDXR were set to 30250212; 28965846; 29040572; 33348459; 37046037; 37481223 Phenotypes for gene: FDXR were set to Neurodevelopmental disorder with mitochondrial abnormalities, optic atrophy, and developmental regression, MIM# 620887 Review for gene: FDXR was set to GREEN Added comment: Multiple reports of individuals with extra-ocular features, including ID and regression; microcephaly. Ataxia reported in multiple individuals, largely paediatric. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.23 | TUBA4A |
Bryony Thompson gene: TUBA4A was added gene: TUBA4A was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: TUBA4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TUBA4A were set to 38884572; 37418012 Phenotypes for gene: TUBA4A were set to Hereditary ataxia MONDO:0100309, TUBA4A-related Mode of pathogenicity for gene: TUBA4A was set to Other Review for gene: TUBA4A was set to GREEN Added comment: PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Spasticity was present in 7/12, 58.3%, cognitive decline in 4/12, 33,3%, and amyotrophy or upper limb muscular weakness in 2/12, 16.6%. 2 patients with p.Pro173Arg also had learning disabilities. 5 cases were confirmed de novo for the variants. Enrichment of rare missense in an ataxia cohort from UK 100k genomes - 6/1103 cases vs 2/20,904 controls, OR = 57.0847 [10.2- 576.7], p = 4.02e-7. Cultured fibroblasts from 3 patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organisation and dynamics, suggestive of a dominant negative mechanism of disease. PMID: 37418012 - 2 Italian spastic ataxia families with p.Glu415Lys, one family segregating the variant in 11 affected individuals and one de novo. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.20 | DAGLA |
Zornitza Stark gene: DAGLA was added gene: DAGLA was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: DAGLA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DAGLA were set to 35737950 Phenotypes for gene: DAGLA were set to Neuroocular syndrome 2, paroxysmal type, MIM# 168885 Review for gene: DAGLA was set to GREEN Added comment: 9 individuals from 8 families reported with daily paroxysmal spells characterized by eye deviation or nystagmus with abnormal head posturing apparent from birth or early infancy. The episodes tend to be triggered after sleeping, and most patients show improvement of the ocular symptoms over time. Affected individuals also have hypotonia, mild developmental delay, dysarthria, and gait ataxia; most have mildly impaired intellectual development. Seizures are not observed. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.17 | COQ4 | Zornitza Stark edited their review of gene: COQ4: Added comment: PMIDs 36047608;38014483;38013626: more than 10 families reported with more limited spastic ataxia phenotype, onset from infancy to adulthood.; Changed publications: 30225196, 33704555, 30847826, 36047608, 38014483, 38013626; Changed phenotypes: Coenzyme Q10 deficiency, primary, 7, MIM# 616276, Spastic ataxia 10, autosomal recessive, MIM# 620666 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.16 | SLC13A3 |
Daniel Flanagan gene: SLC13A3 was added gene: SLC13A3 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC13A3 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200101 (No PMID) Phenotypes for gene: SLC13A3 were set to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate (MIM# 618384) Review for gene: SLC13A3 was set to GREEN Added comment: Seven patients reported with biallelic SLC13A3 variants, causing acute reversible leukoencephalopathy and α-ketoglutarate accumulation. Patients presented with acute neurological deterioration after a febrile illness. 5/7 with ataxia, 4/7 had seizures, 1/7 developmental delay. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.15 | PRICKLE1 | Zornitza Stark edited their review of gene: PRICKLE1: Added comment: LIMITED by ClinGen for AR PME.; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.14 | PRICKLE1 | Zornitza Stark edited their review of gene: PRICKLE1: Added comment: Note most reported variants are missense with little further supportive evidence and ClinVar variants in this gene are all VOUS/LB/B.; Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.12 | ACBD6 |
Lucy Spencer gene: ACBD6 was added gene: ACBD6 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: ACBD6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACBD6 were set to 37951597 Phenotypes for gene: ACBD6 were set to Neurodevelopmental disorder (MONDO#0700092), ACBD6-related Review for gene: ACBD6 was set to GREEN Added comment: PMID: 37951597 45 individuals from 28 families with a neurodevelopmental syndrome with complex and progressive movement disorder phenotype. 18 PTCs and splice, 1 missense 1 in frame insertion. Phenotypes: weight was >50th percentile in 20/34 patients, all mod-severe GDD, facial dysmorphism in 38/40, mild cerebellar ataxia 35/41, limb spasticity/hypertonia 31/41, gait abnormalities in 33/35, dystonia in 30/31. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.11 | ATP2B2 |
Andrew Fennell gene: ATP2B2 was added gene: ATP2B2 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: ATP2B2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ATP2B2 were set to PMID: 37675773 Phenotypes for gene: ATP2B2 were set to Neurodevelopmental Disorder, MONDO:0700092, ATP2B2-related Mode of pathogenicity for gene: ATP2B2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: ATP2B2 was set to GREEN Added comment: 7 unrelated individuals reported with a variable phenotype including dystonia, ataxia, intellectual disability, behavioural symptoms, and seizures. All patients have either missense variants or frameshift variants in the penultimate exon not expected to lead to NMD. This is in contrast to patients with isolated deafness previously reported to have nonsense, frameshift, or splice-site variants outside of this region. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.10 | AGTPBP1 |
Zornitza Stark gene: AGTPBP1 was added gene: AGTPBP1 was added to Ataxia - paediatric. Sources: Expert Review Mode of inheritance for gene: AGTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AGTPBP1 were set to 30420557 Phenotypes for gene: AGTPBP1 were set to Early onset cerebellar atrophy, developmental delay, and feeding and respiratory difficulties, severe motor neuronopathy; Neurodegeneration, childhood-onset, with cerebellar atrophy, 618276 Review for gene: AGTPBP1 was set to GREEN Added comment: Thirteen individuals with bi-allelic variants in this gene, complex neurological phenotype of dev delay/ID, cerebellar atrophy and neuropathy, severe progressive course in six. Sources: Expert Review |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v1.3 | TPR |
Zornitza Stark gene: TPR was added gene: TPR was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: TPR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TPR were set to 34494102 Phenotypes for gene: TPR were set to Multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, TPR-related Review for gene: TPR was set to RED Added comment: Two siblings harbouring variants c.6625C>T/ p.Arg2209Ter (identified in heterozygous state in both siblings and father) and c.2610 + 5G > A (identified in heterozygous state in both siblings and mother) were reported with ataxia, microcephaly and severe intellectual disability. Functional analyses in patient fibroblasts provide evidence that the variants affect TPR splicing, reduce steady-state TPR levels, abnormal nuclear pore composition and density, and altered global RNA distribution. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.346 | FRMD5 |
Zornitza Stark gene: FRMD5 was added gene: FRMD5 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: FRMD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FRMD5 were set to 36206744 Phenotypes for gene: FRMD5 were set to Neurodevelopmental disorder MONDO:0700092, FRMD5-related Review for gene: FRMD5 was set to GREEN Added comment: Eight individuals reported with missense variants in this gene, de novo in 6 where parents were available. Clinical presentation was with ID, seizures, ataxia. Fly model. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.344 | LETM1 |
Ee Ming Wong gene: LETM1 was added gene: LETM1 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: LETM1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LETM1 were set to 36055214 Phenotypes for gene: LETM1 were set to Mitochondrial disease MONDO#0044970, LETM1-related Review for gene: LETM1 was set to GREEN gene: LETM1 was marked as current diagnostic Added comment: -18 affected individuals from 11 unrelated families harbouring ultra-rare bi-allelic missense and loss-of-function LETM1 variants -Most of the affected individuals (14/18, 78%) had an infantile-onset disease manifestation, and 4/18 (22%) presented first symptoms between the ages of 1.5 and 2 years -Variant types included missense, frameshift, stop loss, in-frame deletion and splice defect -From biochemical and morphological studies, bi-allelic LETM1 variants are associated with defective mitochondrial K efflux, swollen mitochondrial matrix structures, and loss of important mitochondrial oxidative phosphorylation protein components Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.340 | UCHL1 | Zornitza Stark edited their review of gene: UCHL1: Added comment: PMID 35986737: 34 individuals from 18 unrelated families, carrying 13 heterozygous loss-of-function variants (15 families) and an inframe insertion (3 families). Affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17).; Changed publications: 28007905, 23359680, 11555633, 35986737; Changed phenotypes: Spastic paraplegia 79, autosomal recessive, MIM#615491, Neurodegenerative disease, MONDO:0005559, UCHL1-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.333 | PRKCG |
Zornitza Stark gene: PRKCG was added gene: PRKCG was added to Ataxia - paediatric. Sources: Expert Review Mode of inheritance for gene: PRKCG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PRKCG were set to 34292398 Phenotypes for gene: PRKCG were set to Spinocerebellar ataxia 14, MIM# 605361 Review for gene: PRKCG was set to AMBER Added comment: Typically adult onset, but note two individuals reported with severe paediatric onset. Sources: Expert Review |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.331 | CACNA2D2 |
Ain Roesley gene: CACNA2D2 was added gene: CACNA2D2 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: CACNA2D2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CACNA2D2 were set to 23339110; 24358150; 30410802; 29997391; 31402629 Phenotypes for gene: CACNA2D2 were set to Cerebellar atrophy with seizures and variable developmental delay MIM#618501 Review for gene: CACNA2D2 was set to GREEN gene: CACNA2D2 was marked as current diagnostic Added comment: 4 out of 6 families reported individuals <1 years old with ataxia Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.330 | SUFU | Alison Yeung Added comment: Comment on list classification: Associated with paediatric-onset ataxia with oculomotor apraxia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.329 | SUFU |
Alison Yeung gene: SUFU was added gene: SUFU was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: SUFU was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SUFU were set to 33024317 Phenotypes for gene: SUFU were set to congenital ocular motor apraxia (forme fruste of Joubert syndrome) Review for gene: SUFU was set to GREEN gene: SUFU was marked as current diagnostic Added comment: Clinical features include congenital oculomotor apraxia, hypotonia, ataxia and mild DD, and only a third manifested intellectual disability of variable severity. Brain MRI shows consistent findings characterised by vermis hypoplasia, superior cerebellar dysplasia and subtle-to-mild abnormalities of the superior cerebellar peduncles. SUFU-associated Basal cell nevus syndrome (Gorlin) are likely allelic disorders, as there is currently no convincing evidence for a clinical overlap. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.327 | KCND3 |
Zornitza Stark gene: KCND3 was added gene: KCND3 was added to Ataxia - paediatric. Sources: Expert Review Mode of inheritance for gene: KCND3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCND3 were set to 32823520 Phenotypes for gene: KCND3 were set to Spinocerebellar ataxia 19, MIM# 607346 Review for gene: KCND3 was set to GREEN Added comment: Variable age of symptom onset, including paediatric. Reviewed in PMID 32823520. Sources: Expert Review |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.325 | ATP6V0A1 |
Chern Lim gene: ATP6V0A1 was added gene: ATP6V0A1 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: ATP6V0A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ATP6V0A1 were set to PMID:34909687 Phenotypes for gene: ATP6V0A1 were set to Neurodevelopmental disorder, MONDO:0700092, ATP6V0A1-associated Review for gene: ATP6V0A1 was set to GREEN gene: ATP6V0A1 was marked as current diagnostic Added comment: PMID: 34909687 - 17 individuals from 14 unrelated families: 5 affected individuals with biallelic variants, presented with early-onset progressive myoclonus epilepsy with ataxia; 12 individuals carried de novo missense variants and showed severe developmental and epileptic encephalopathy. - The mean age of onset was 11.8+/-7.5 years for individuals carrying the compound heterozygous variants and 5.8+/-4.2 months for individuals with the de novo variants. - The R740Q variant, which alone accounts for ~50% of the mutations identified among our cases, leads to failure of lysosomal hydrolysis by directly impairing acidification of the endolysosomal compartment, causing autophagic dysfunction and severe developmental defect in C. elegans. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.324 | WARS2 |
Zornitza Stark gene: WARS2 was added gene: WARS2 was added to Ataxia - paediatric. Sources: Expert Review Mode of inheritance for gene: WARS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WARS2 were set to 29120065; 31970218; 34890876; 28236339; 28650581; 28905505; 30920170 Phenotypes for gene: WARS2 were set to Parkinsonism-dystonia 3, childhood-onset, MIM# 619738; Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, MIM# 617710 Review for gene: WARS2 was set to GREEN Added comment: Childhood-onset parkinsonism-dystonia-3 (PKDYS3) is an autosomal recessive neurodegenerative disorder with onset in infancy or early childhood. Affected individuals present with progressive movement abnormalities, including parkinsonism with tremor, dystonia, myoclonus ataxia, and hyperkinetic movements such as ballismus. The parkinsonism features may be responsive to treatment with levodopa, although many patients develop levodopa-induced dyskinesia. Some patients may have mild cognitive impairment or psychiatric disturbances. 8 individuals from 4 families reported. NEMMLAS is an autosomal recessive multisystemic disorder characterized by delayed psychomotor development, intellectual disability, and abnormal motor function, including hypotonia, dystonia, ataxia, and spasticity. Patient tissues may show deficiencies in one or more of the mitochondrial oxidative phosphorylation (OXPHOS) enzymes, but this is not a constant finding. 12 individuals from 8 unrelated families reported. It is unclear whether these are two distinct disorders or whether they represent a spectrum of severity for a single condition. Sources: Expert Review |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.319 | TBCE |
chirag patel gene: TBCE was added gene: TBCE was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TBCE were set to PubMed: 27666369 Phenotypes for gene: TBCE were set to Encephalopathy, progressive, with amyotrophy and optic atrophy, OMIM #617207 Review for gene: TBCE was set to GREEN Added comment: 5 patients from 3 unrelated Italian families with progressive encephalopathy with amyotrophy and optic atrophy (PEAMO), and biallelic variants in TCBE gene (WES or Sanger). PEAMO is a severe autosomal recessive neurodegenerative disorder characterized by delayed development with hypotonia apparent in infancy and subsequent motor regression. Most affected individuals are unable to or lose the ability to sit and show distal amyotrophy and weakness of all 4 limbs. The patients are cognitively impaired and unable to speak or have severe dysarthria. Additional features include optic atrophy, thin corpus callosum, and cerebellar atrophy. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.318 | PIK3R5 |
chirag patel gene: PIK3R5 was added gene: PIK3R5 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: PIK3R5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIK3R5 were set to PubMed: 22065524 Phenotypes for gene: PIK3R5 were set to Ataxia-oculomotor apraxia 3, OMIM #615217 Review for gene: PIK3R5 was set to RED Added comment: Al Tassan et al. (2012) reported 4 sibs, from consanguineous Saudi Arabian family, with ataxia-oculomotor apraxia. The proband developed progressive unsteady gait and had frequent falls at age 14 years with later onset of arm dysmetria and dysarthria. He became wheelchair-bound at age 23. Ocular movement was impaired, with slowed saccadic eye movements and head-eye lag resulting in head thrust, but smooth pursuit was normal. He had severe limb and axial dysmetria with mild distal atrophy and weakness affecting the lower limbs more than the upper limbs. He also had distal sensory impairment, more prominent in the lower limbs, areflexia, and axonal sensory polyneuropathy with absent sensory nerve action potentials in the lower limbs. Laboratory studies showed increased level of alpha-fetoprotein, and brain MRI showed atrophy of the cerebellar folia and vermis. His 3 sibs were similarly affected. A homozygous mutation in the PIK3R5 gene (P629S) was found by linkage analysis followed by sequencing of the genes within the region. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.316 | PIGS |
chirag patel gene: PIGS was added gene: PIGS was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: PIGS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PIGS were set to PubMed: 30269814, 33410539 Phenotypes for gene: PIGS were set to Developmental and epileptic encephalopathy 95, OMIM # 618143 Review for gene: PIGS was set to GREEN Added comment: DEE95 is a severe autosomal recessive developmental disorder characterized by severely impaired global development, hypotonia, weakness, ataxia, coarse facial features, and intractable seizures. Mutiple patients reported with biallelic variants. Some functional evidence with decreased levels of GPI-anchored proteins compared to controls. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.314 | NUBPL |
chirag patel gene: NUBPL was added gene: NUBPL was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: NUBPL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUBPL were set to PubMed: 23553477, 32518176, Phenotypes for gene: NUBPL were set to Mitochondrial complex I deficiency, nuclear type 21, OMIM # 618242 Review for gene: NUBPL was set to GREEN Added comment: Many patients reported with biallelic variants in gene with mitochondrial complex I deficiency. Presents with various neurodevelopmental issues including ataxia. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.312 | NOVA2 |
chirag patel gene: NOVA2 was added gene: NOVA2 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: NOVA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NOVA2 were set to PMID: 32197073 Phenotypes for gene: NOVA2 were set to Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities, OMIM #618859 Review for gene: NOVA2 was set to GREEN Added comment: Six individuals with de novo frameshift variants resulting in C-terminal extension suggesting partial LoF as mechanism. Early-onset neurologic disorder characterized by global developmental delay, poor or absent speech and language development, and behavioral abnormalities reminiscent of autism spectrum disorder. Additional features may include poor overall growth with small head circumference, axial hypotonia, spasticity, and seizures. Some patients have abnormal findings on brain imaging, including cerebral atrophy, cerebellar atrophy, and/or thin corpus callosum. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.307 | CHP1 |
chirag patel gene: CHP1 was added gene: CHP1 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: CHP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CHP1 were set to PMID: 29379881, 32787936 Phenotypes for gene: CHP1 were set to Spastic ataxia 9, autosomal recessive, OMIM #618438 Review for gene: CHP1 was set to GREEN Added comment: 2 different consanguineous families with 2 affected siblings with ataxia (1 paediatric onset, 1 adult onset). 3 of the patients had cerebellar atrophy. WES identified homozygous variants in CHP1 gene in both families (K19del and Arg91Cys), which segregated with the disorder in the family. Decreased CHP1 protein on IHC of cerebellar tissue in family with Arg91Cys variant. In vitro functional expression studies in HEK293 cells showed that the K19del mutation resulted in decreased protein expression, with normal levels of transcript, suggesting defects in protein stability. The mutant protein formed massive protein aggregates in transfected neuronal cell bodies and neurite-like projections, whereas the wildtype protein showed a more uniform distribution. The mutant protein altered CHP1 association into functional complexes and impaired membrane localization of the Na+/H+ transporter NHE1. The findings indicated that the CHP1 mutation likely causes ataxia in an NHE1-dependent manner, resembling the mechanism observed in the Chp1 vacillator mutant mouse. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.305 | BRAT1 |
chirag patel gene: BRAT1 was added gene: BRAT1 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: BRAT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BRAT1 were set to PMID: 26483087, 26494257, 27282546 Phenotypes for gene: BRAT1 were set to Neurodevelopmental disorder with cerebellar atrophy and with or without seizures, MIM#618056 Review for gene: BRAT1 was set to GREEN Added comment: At least 4 individuals reported from unrelated families and bi-allelic variants in this gene. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.301 | GEMIN5 |
chirag patel gene: GEMIN5 was added gene: GEMIN5 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: GEMIN5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GEMIN5 were set to PMID: 34569062, 33963192 Phenotypes for gene: GEMIN5 were set to Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction, OMIM # 619333 Review for gene: GEMIN5 was set to GREEN Added comment: Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (NEDCAM) is an autosomal recessive disorder characterized by global developmental delay with prominent motor abnormalities, mainly axial hypotonia, gait ataxia, and appendicular spasticity. Affected individuals have cognitive impairment and speech delay; brain imaging shows cerebellar atrophy. 30 individuals from 22 unrelated families reported by Kour et al (2021). Saida et al (2021) report compound heterozygous GEMIN5 variants in 2 individuals with cerebellar atrophy/hypoplasia. Three novel truncating variants and one previously reported missense variant were identified. Western blotting analysis using lymphoblastoid cell lines derived from both affected individuals showed significantly reduced levels of GEMIN5 protein. Zebrafish model for null variants p.(Arg733Thrfs*6) and p.(Ala1305Leufs*14) exhibited complete lethality at 2 weeks and recapitulated a distinct dysplastic phenotype. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.297 | DHDDS |
Zornitza Stark gene: DHDDS was added gene: DHDDS was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: DHDDS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DHDDS were set to 29100083; 33798445; 34182312; 34382076 Phenotypes for gene: DHDDS were set to Developmental delay and seizures with or without movement abnormalities, OMIM:617836 Review for gene: DHDDS was set to GREEN Added comment: Monoallelic variants are associated with a neurodevelopmental disorder comprising infantile or childhood-onset DD/ID, epilepsy and a variable movement phenotype which typically initially manifests as action myoclonus/cortical tremor and in some cases ataxia - at least 11 unrelated cases of ataxia reported in literature. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.295 | COQ4 |
Zornitza Stark gene: COQ4 was added gene: COQ4 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: COQ4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COQ4 were set to 30225196; 33704555; 30847826 Phenotypes for gene: COQ4 were set to Coenzyme Q10 deficiency, primary, 7, MIM# 616276; Childhood-onset ataxia Review for gene: COQ4 was set to GREEN Added comment: At least 6 individuals from 4 families reported as having ataxia. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.292 | DAB1 |
Daniel Flanagan gene: DAB1 was added gene: DAB1 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: DAB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DAB1 were set to PMID: 33928188 Phenotypes for gene: DAB1 were set to epilepsy; developmental delay; cerebellar ataxia; structural brain abnormalities; oral motor difficulty Penetrance for gene: DAB1 were set to unknown Review for gene: DAB1 was set to AMBER Added comment: WES trio analysis identified compound heterozygous DAB1 canonical splice variants in a child with epilepsy (onset 6 years), developmental delay, cerebellar ataxia, oral motor difficulty, and structural brain abnormalities. RT-PCR confirms that the first variant (c.307-2A>T) causes a in-frame deletion of 3 amino acids. The second variant (c.67+1G>T) is reported to causes an in-frame deletion of exon 4 (first coding exon) and loss of the ATG initiation site. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.291 | RFXANK |
Elena Savva gene: RFXANK was added gene: RFXANK was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: RFXANK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RFXANK were set to PMID: 33855173; 23314770; 28676232 Phenotypes for gene: RFXANK were set to Progressive Ataxia and Neurologic Regression; MHC class II deficiency, complementation group B MIM#209920 Review for gene: RFXANK was set to AMBER Added comment: PMID: 33855173 - 1 family (2 affecteds, 3rd not sequenced) with a homozygous c.271+1G>C splice variant, late-onset immunodeficiency and subacute progressive neurodegenerative disease, including cognition, motor, visual and cerebellar features. MRI demonstrated global cerebral and cerebellar atrophy. PMID: 23314770 - 1/34 MHCII deficient patients with biallelic variants reported with ataxia. Majority of patients (including patient with ataxia) share a founder variant (c.338-25_338del26). PMID: 28676232 - single 30 month old patient with ataxic gait and dysarthria and a homozygous PTC. Summary: 3 patients but uncommon feature, variable expressivity Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.290 | RNF220 |
Zornitza Stark gene: RNF220 was added gene: RNF220 was added to Ataxia - paediatric. Sources: Literature founder tags were added to gene: RNF220. Mode of inheritance for gene: RNF220 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNF220 were set to 33964137; 10881263 Phenotypes for gene: RNF220 were set to Leukodystrophy; CNS hypomyelination; Ataxia; Intellectual disability; Sensorineural hearing impairment; Elevated hepatic transaminases; Hepatic fibrosis; Dilated cardiomyopathy; Spastic paraplegia; Dysarthria; Abnormality of the corpus callosum Review for gene: RNF220 was set to GREEN Added comment: Sferra et al (2021 - PMID: 33964137) provide extensive evidence that biallelic RNF220 mutations cause a disorder characterized by hypomyelinating leukodystrophy, ataxia (9/9 - onset 1-5y), borderline intellectual functioning (3/9) / intellectual disability (5/9 - in most cases mild), sensorineural deafness (9/9) with complete hearing loss in the first decade of life, hepatopathy (9/9) with associated periportal fibrosis, and dilated cardiomyopathy (9/9) which was fatal. Other neurologic manifestations apart from ataxia incl. hyperreflexia (8/8), spastic paraplegia (9/9), dysarthria (9/9), peripheral neuropathy (4/9), seizures in one case (1/9). Upon brain MRI there was thin corpus callosum (9/9) or cerebellar atrophy in some (2/9). The authors identified homozygosity for 2 recurrent missense RNF220 variants in affected members belonging to these 5 broad consanguineous pedigrees (7 families), namely NM_018150.4:c.1094G>A / p.Arg365Gly in 4 Roma families in the context of a shared haplotype (/founder effect) as well as c.1088G>A / p.Arg363Gly in a large pedigree from southern Italy initially reported by Leuzzi et al (2000 - PMID: 10881263). Extensive segregation analyses were carried out including several affected and unaffected members. RNF220 encodes ring finger protein 220, which functions as an E3 ubiquitin ligase. Previous studies have shown among others a role in modulation of Sonic hedgehog/GLI signaling and cerebellar development Evidence for the role of RNF220 included relevant expression, localization within the cell, interaction partners (lamin B1, 20S proteasome), similarities with other laminopathies in terms of phenotype, etc : *RNF220 has a relevant expression pattern in CNS (based on qRT-PCR analyses in human brain, cerebellum, cerebral cortex / mRNA levels in human fetal CNS with higher expression in cerebellum, spinal cord and cortex / previous GTEx data / protein levels in mouse CNS) *The protein displays nuclear localization based on iPSC cells differentiated to motor neurons (also supported by data from the Human Protein Atlas). Transfection of COS-1 cells demonstrated localization primarily to the nucleus (as also previously demonstrated in HEK293T cells) in vesicle like structures with ASF2/SF2 colocalization suggesting enrichment in nuclear speckles. There was also partial co-distribution with the 20S proteasome. R363Q and R365Q additionally coalesced in the cytoplasm forming protein aggregates/inclusions. *Immunofluorescence studies in patient fibroblasts also confirmed abnormal increase of the protein in the cytoplasm and increased fluorescence with the 20S proteasome. *Proteomic identification of RNF220-interacting proteins in transfected HEK293T cells demonstrated enrichment for all members of the lamin protein family (incl . lamin B1, AC, B2). *RNAi-mediated downregulation of RNF222 in Drosophila suggested altered subcellular localization and accumulation of the fly orthologue for human lamin B1. *Immunoprecipitation of lamin B1 from the nuclear matrix of cerebellar cells suggested significant interaction of endogenous lamin B1 with RNF220, while transfection studies in HEK293T cells for wt/mt suggested reduced binding to endogenous lamin B1 for RNF220 mt compared to wt (more prominent for R365Q). RNF220 mutants also reduced ubiquitination of nuclear lamin B1 compared to wt. *Patient fibroblasts immunostained with different nuclear envelope markers displayed abnormal nuclear shapes with multiple invaginations and lobulations, findings also observed in laminopathies. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.288 | PRDX3 |
Zornitza Stark gene: PRDX3 was added gene: PRDX3 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: PRDX3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRDX3 were set to 33889951 Phenotypes for gene: PRDX3 were set to Cerebellar ataxia (early onset, mild to moderate, progressive) Review for gene: PRDX3 was set to GREEN Added comment: Biallelic variants in 5 unrelated families with early onset (median 21 years , range 13-22 years) with ataxia with variable additional hyper- and hypokinetic movement disorders, and severe early-onset cerebellar atrophy (seen on MRI), and involvement of the brainstem, medullary olive and parietal cortex. Evolution of the disease was gait ataxia leading to upper limb ataxia, then dysarthria and then dysphagia, all within a decade. For some of these patients, the phenotype included myoclonus, dystonia and / or tremor. Mild classical mitochondrial features were seen in one of the patients, namely ptosis and COX-negative fibres. The variants were homozygous nonsense, homozygous frameshift, homozygous missense, and a compound heterozygote with a splice variant and missense, all leading to complete loss of the protein. Oxidative stress and mitochondrial dysfunction was indicated as the disease mechanism. The families originated from Germany, France, India and two from eastern Turkey. The two families from Turkey were seemingly unrelated to each other but had the same homozygous missense. Patient fibroblasts from each of the five probands showed lack of protein (via Western blot) and decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity. PRDX3 encodes peroxiredoxin 3, a mitochondrial antioxidant protein, that catalyses the reduction of hydrogen peroxide. It localises in the mitochondria, where most hydrogen peroxide is generated. Functional studies: PRDX3 knockdown (induced by silencing RNA against PRDX3) in cerebellar medulloblastoma cells showed significantly decreased cell viability, increased hydrogen peroxide levels and increased susceptibility to apoptosis triggered by reactive oxygen species. In addition, induced knockdown drosophila (in vivo animal model) had aberrant locomotor phenotypes and reduced lifespans, while immunolabelling of the brain showed increased cell death after exposure to oxidative stress. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.286 | ATG7 |
Zornitza Stark gene: ATG7 was added gene: ATG7 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: ATG7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATG7 were set to 34161705 Phenotypes for gene: ATG7 were set to Spinocerebellar ataxia, SCAR31, MIM#619422 Review for gene: ATG7 was set to GREEN Added comment: 12 individuals from 5 unrelated families reported with a complex neurodevelopmental disorder and bi-allelic variants in this gene. Age range from 21 months to 71 years of age. Main clinical features included axial hypotonia, variably impaired intellectual development with poor or absent speech, and delayed walking (up to 7 years of age) or inability to walk. All had ataxia, often with tremor or dyskinesia, as well as dysarthria associated with cerebellar hypoplasia on brain imaging. Most had optic atrophy, and some had ptosis, chronic progressive external ophthalmoplegia, retinopathy, and strabismus; 1 had early-onset cataracts. The ore severely affected individuals had spastic paraplegia and inability to walk. Functional data including mouse model. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.281 | POU4F1 |
Bryony Thompson gene: POU4F1 was added gene: POU4F1 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: POU4F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POU4F1 were set to 33783914; 8876243 Phenotypes for gene: POU4F1 were set to Ataxia; intention tremor; hypotonia Review for gene: POU4F1 was set to GREEN Added comment: 4 unrelated probands presenting with paediatric onset ataxia, intention tremor, and hypotonia, with de novo loss of function variants, and supporting null mouse model. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.279 | SLC25A46 |
Zornitza Stark changed review comment from: Hereditary motor and sensory neuropathy type VIB is an autosomal recessive complex progressive neurologic disorder characterized mainly by early-onset optic atrophy resulting in progressive visual loss and peripheral axonal sensorimotor neuropathy with highly variable age at onset and severity. Affected individuals also have cerebellar or pontocerebellar atrophy on brain imaging, and they show abnormal movements, such as ataxia, dysmetria, and myoclonus. At least 10 unrelated families reported, supportive functional data.; to: Hereditary motor and sensory neuropathy type VIB is an autosomal recessive complex progressive neurologic disorder characterized mainly by early-onset optic atrophy resulting in progressive visual loss and peripheral axonal sensorimotor neuropathy with highly variable age at onset and severity. Affected individuals also have cerebellar or pontocerebellar atrophy on brain imaging, and they show abnormal movements, such as ataxia, dysmetria, and myoclonus. New PCH disease entity added by OMIM in 2021 to reflect the more severe end of the spectrum. At least 10 unrelated families reported, supportive functional data. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.278 | VPS41 |
Zornitza Stark gene: VPS41 was added gene: VPS41 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: VPS41 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS41 were set to 32808683; 33764426 Phenotypes for gene: VPS41 were set to Dystonia; intellectual disability; ataxia; cerebellar atrophy Review for gene: VPS41 was set to GREEN Added comment: 10 individuals from 6 unrelated families reported with a progressive neurodevelopmental disorder. Affected individuals were born after uneventful pregnancies and presented in most cases early in life with developmental delay. Various degrees of ataxia, hypotonia, and dystonia developed in all affected individuals, preventing independent ambulation. Likewise, nystagmus was commonly described. In addition, all affected individuals displayed intellectual disability and speech delay, and one sib pair had treatment-resistant epilepsy. Brain MRI revealed mild cerebellar atrophy and vermian atrophy without other major structural abnormalities in most affected individuals. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.268 | SATB1 |
Elena Savva gene: SATB1 was added gene: SATB1 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: SATB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SATB1 were set to PMID: 33513338; 33057194 Phenotypes for gene: SATB1 were set to Neurodevelopmental disorders Mode of pathogenicity for gene: SATB1 was set to Other Review for gene: SATB1 was set to GREEN Added comment: PMID: 33513338: 42 patients with SNVs. 28 de novo, 3 inherited from an affected parent. Missense variants - more severe, profound ID NMD PTCs - milder disease Functional studies show missense variants have a STRONGER binding to downstream targets Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.268 | KCNN2 |
Ain Roesley gene: KCNN2 was added gene: KCNN2 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: KCNN2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: KCNN2 were set to 33242881 Phenotypes for gene: KCNN2 were set to neurodevelopmental movement disorders Penetrance for gene: KCNN2 were set to unknown Review for gene: KCNN2 was set to GREEN Added comment: - 11 probands all de novo except for 1 mother-daughter pair. - a mix of null and missense variants - 2/11 with microcephaly, 10/11 motor delay, 7/11 language delay (excluding 2 with regression), all with varying degrees of ID, 3/11 seizures, 7/11 movement disorder, 4/11 cerebellar ataxia, 6/11 MRI anomalies additional variants were noted in 2 patients: 1x cHet for variants in MED12L and 1x de novo TNK2 variant patch clamp functional studies were also done Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.267 | CBY1 |
Bryony Thompson gene: CBY1 was added gene: CBY1 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: CBY1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CBY1 were set to 33131181; 25103236; 25220153 Phenotypes for gene: CBY1 were set to intellectual disability; cerebellar ataxia; molar tooth sign; polydactyly; Joubert syndrome Review for gene: CBY1 was set to GREEN Added comment: Three cases in two unrelated consanguineous families with homozygous loss of function variants, with ataxia as a feature of the condition. Multiple null model organisms recapitulate the human phenotype: Null mouse model had cystic kidneys, a phenotype common to ciliopathies. Reducing Cby levels in Xenopus laevis model reduced the density of multiciliated cells, the number of basal bodies per multiciliated cell, and the numbers of neural tube primary cilia; it also led to abnormal development of the neural crest, central nervous system, and pronephros. Depletion of cby1 in zebrafish results in ciliopathy‐related phenotypes. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.265 | MTCL1 | Bryony Thompson edited their review of gene: MTCL1: Added comment: A new report of another case with a homozygous loss of function variant and a similar phenotype to the previously reported early onset homozygous Polish case (2 independent cases), and the supporting null mouse model.; Changed rating: GREEN; Changed publications: 30548255, 28283581, 32961396; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.263 | NUS1 |
Elena Savva gene: NUS1 was added gene: NUS1 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: NUS1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: NUS1 were set to PMID: 31656175; 29100083 Phenotypes for gene: NUS1 were set to Epilepsy, myoclonus, ataxia and scoliosis; ?Congenital disorder of glycosylation, type 1aa, 617082; Mental retardation, autosomal dominant 55, with seizures, 617831 Review for gene: NUS1 was set to GREEN Added comment: PMID: 31656175 - 2 unrelated patients with the same de novo splice variant and ataxia. Splice variant undergoes partial NMD. PMID: 29100083 - 3 unrelated patients w/ 2 PTCs and an inframe exon 2 deletion. Only 1/3 was reported to have ataxia Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.262 | MAG | Zornitza Stark edited their review of gene: MAG: Added comment: Four more individuals reported with variable combinations of psychomotor delay, ataxia, eye movement abnormalities, spasticity, dystonia, and neuropathic symptoms.; Changed publications: 32629324, 32340215, 32629324; Changed phenotypes: Spastic paraplegia 75, autosomal recessive, MIM# 616680, Cerebellar ataxia, Oculomotor apraxia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.261 | CAD |
chirag patel gene: CAD was added gene: CAD was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: CAD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CAD were set to PMID: 32820246 Phenotypes for gene: CAD were set to Epileptic encephalopathy, early infantile, 50; OMIM # 616457 Review for gene: CAD was set to GREEN gene: CAD was marked as current diagnostic Added comment: 2020 series: 6/20 patients reported had ataxia relating to cerebellar atrophy, which is an expansion to the phenotype. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.258 | MAG |
Zornitza Stark gene: MAG was added gene: MAG was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: MAG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAG were set to 32629324; 32340215 Phenotypes for gene: MAG were set to Spastic paraplegia 75, autosomal recessive, MIM# 616680; Cerebellar ataxia; Oculomotor apraxia Review for gene: MAG was set to GREEN Added comment: At least 5 families reported where ataxia was a prominent feature. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.257 | UCHL1 |
Zornitza Stark changed review comment from: Ataxia is part of the phenotype. Sources: Expert list; to: Ataxia is part of the phenotype. Two unrelated families and a mouse model. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.257 | SVBP |
Zornitza Stark changed review comment from: 5 unrelated families with homozygous mutations in SVBP; syndromic cause of paediatric ataxia. The mutations segregated with the disorder in all families. In vitro functional cellular expression studies showed that protein levels of the SVBP mutants were barely detectable, suggesting instability, and that the mutant proteins had lost VASH/SVBP catalytic detyrosination activity toward tubulin. Knockdown of about 50% Svbp expression using shRNA in rat hippocampal neurons impaired the formation of excitatory synapses compared to controls. Sources: Literature; to: 5 unrelated families with homozygous mutations in SVBP; syndromic cause of paediatric ataxia. Some shared the same founder variant, p.Q28*. The mutations segregated with the disorder in all families. In vitro functional cellular expression studies showed that protein levels of the SVBP mutants were barely detectable, suggesting instability, and that the mutant proteins had lost VASH/SVBP catalytic detyrosination activity toward tubulin. Knockdown of about 50% Svbp expression using shRNA in rat hippocampal neurons impaired the formation of excitatory synapses compared to controls. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.257 | SLC52A2 | Zornitza Stark changed review comment from: Generally presents with a range of neuropathies but ataxia described.; to: Generally presents with a range of neuropathies but ataxia described. Treatable condition. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.255 | SLC25A46 |
Zornitza Stark changed review comment from: Hereditary motor and sensory neuropathy type VIB is an autosomal recessive complex progressive neurologic disorder characterized mainly by early-onset optic atrophy resulting in progressive visual loss and peripheral axonal sensorimotor neuropathy with highly variable age at onset and severity. Affected individuals also have cerebellar or pontocerebellar atrophy on brain imaging, and they show abnormal movements, such as ataxia, dysmetria, and myoclonus. Nine unrelated families reported, supportive functional data.; to: Hereditary motor and sensory neuropathy type VIB is an autosomal recessive complex progressive neurologic disorder characterized mainly by early-onset optic atrophy resulting in progressive visual loss and peripheral axonal sensorimotor neuropathy with highly variable age at onset and severity. Affected individuals also have cerebellar or pontocerebellar atrophy on brain imaging, and they show abnormal movements, such as ataxia, dysmetria, and myoclonus. At least 10 unrelated families reported, supportive functional data. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.255 | SLC25A46 |
Zornitza Stark changed review comment from: Age of onset is variable, but childhood onset described. Ataxia is a feature.; to: Hereditary motor and sensory neuropathy type VIB is an autosomal recessive complex progressive neurologic disorder characterized mainly by early-onset optic atrophy resulting in progressive visual loss and peripheral axonal sensorimotor neuropathy with highly variable age at onset and severity. Affected individuals also have cerebellar or pontocerebellar atrophy on brain imaging, and they show abnormal movements, such as ataxia, dysmetria, and myoclonus. Nine unrelated families reported, supportive functional data. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.254 | SCYL1 | Zornitza Stark changed review comment from: Childhood onset.; to: Childhood onset, at least 7 unrelated families reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.252 | SCN2A | Zornitza Stark changed review comment from: Classically presents with seizures and DD/ID although a range of other manifestations reported, including movement abnormalities, including ataxia.; to: Classically presents with seizures and DD/ID although a range of other manifestations reported, including movement abnormalities, including ataxia, especially episodic ataxia. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.251 | RUBCN | Zornitza Stark changed review comment from: Two consanguineous families reported in the literature with homozygous truncating variants in this gene and ataxia.; to: Three consanguineous families reported in the literature with homozygous truncating variants in this gene and ataxia. Two have the same founder variant. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.251 | RORA |
Zornitza Stark changed review comment from: 11 unrelated individuals with syndromic intellectual disability and de novo variants in this gene. Severity varied from mild borderline intellectual disability with mild speech delay or normal speech, through to severe cognitive impairment with poor or absent speech. Most had ataxia, hypotonia, poor coordination, and/or mild tremor, suggesting cerebellar dysfunction. Three individuals had documented cerebellar hypoplasia or pontocerebellar atrophy on brain imaging. Seven had seizures of variable types, including neonatal myoclonic, tonic-clonic, multifocal, generalized, and absence. Five were diagnosed with autism spectrum disorder. More variable features included strabismus, esotropia, nystagmus, and oculomotor apraxia; to: 11 unrelated individuals with syndromic intellectual disability and de novo variants in this gene. Severity varied from mild borderline intellectual disability with mild speech delay or normal speech, through to severe cognitive impairment with poor or absent speech. Most had ataxia, hypotonia, poor coordination, and/or mild tremor, suggesting cerebellar dysfunction. Three individuals had documented cerebellar hypoplasia or pontocerebellar atrophy on brain imaging. Seven had seizures of variable types, including neonatal myoclonic, tonic-clonic, multifocal, generalized, and absence. Five were diagnosed with autism spectrum disorder. More variable features included strabismus, esotropia, nystagmus, and oculomotor apraxia. Postulated that some variants exert dominant-negative effect resulting in a more severe phenotype than the LoF variants. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.247 | MORC2 |
Zornitza Stark gene: MORC2 was added gene: MORC2 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: MORC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MORC2 were set to 28402445 Phenotypes for gene: MORC2 were set to Axonal type CMT disease type 2Z, 616688; Cerebellar ataxia Review for gene: MORC2 was set to GREEN Added comment: The p.Thr362Arg variant has been reported as a de novo event in unrelated families with cerebellar ataxia in addition to CMT and nocturnal hypoventilation. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.243 | MAPK8IP3 |
Zornitza Stark changed review comment from: >3 reported individuals and functional evidence in Caenorhabditis elegans Sources: Literature; to: 18 reported individuals of whom 2 had ataxia. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.240 | LAMA1 | Zornitza Stark commented on gene: LAMA1: Five unrelated families reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.240 | KCNA2 | Zornitza Stark commented on gene: KCNA2: Review of 23 affected individuals in PMID 29050392: some variants are LoF and others GoF, and some genotype-phenotype correlations made. The main differences were (i) predominant focal (loss-of-function) versus generalized (gain-of-function) seizures and corresponding epileptic discharges with prominent sleep activation in most cases with loss-of-function mutations; (ii) more severe epilepsy, developmental problems and ataxia, and atrophy of the cerebellum or even the whole brain in about half of the patients with gain-of-function mutations; and (iii) most severe early-onset phenotypes, occasionally with neonatal onset epilepsy and developmental impairment, as well as generalised and focal seizures and EEG abnormalities for patients with gain- and loss-of-function mutations. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.233 | CSTB |
Zornitza Stark changed review comment from: Myoclonic epilepsy of Unverricht and Lundborg is an autosomal recessive disorder characterized by onset of neurodegeneration between 6 and 13 years of age. It is typically progressive in adolescence, with dramatic worsening of myoclonus and ataxia in the first 6 years after onset. The disease stabilises in early adulthood, and myoclonus and ataxia may even improve, and there is minimal to no cognitive decline. Note the most common causative allele is a dodecamer repeat in the promoter region.; to: Myoclonic epilepsy of Unverricht and Lundborg is an autosomal recessive disorder characterized by onset of neurodegeneration between 6 and 13 years of age. It is typically progressive in adolescence, with dramatic worsening of myoclonus and ataxia in the first 6 years after onset. The disease stabilises in early adulthood, and myoclonus and ataxia may even improve, and there is minimal to no cognitive decline. Note the most common causative allele is a dodecamer repeat in the promoter region. Missense variants have been reported, most commonly compound het with the repeat, except for p.Gly4Arg which has been reported in the homozygous state also. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.228 | ATP8A2 |
Zornitza Stark changed review comment from: Multiple individuals from unrelated families reported with bi-allelic variants in this gene and neurological phenotypes including intellectual disability and cerebellar ataxia. Sources: Expert list; to: 10 individuals from six unrelated families reported with bi-allelic variants in this gene and neurological phenotypes including intellectual disability and cerebellar ataxia. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.228 | ATP8A2 |
Zornitza Stark changed review comment from: Multiple individuals from unrelated families reported with bi-allelic variants in this gene and neurological phenotypes including intellectual disability. Sources: Expert list; to: Multiple individuals from unrelated families reported with bi-allelic variants in this gene and neurological phenotypes including intellectual disability and cerebellar ataxia. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.225 | ADPRHL2 | Zornitza Stark Added comment: Comment when marking as ready: New HGNC approved name is ADPRS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.225 | ADPRHL2 | Zornitza Stark Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.225 | ADPRHL2 | Zornitza Stark edited their review of gene: ADPRHL2: Added comment: Fourteen unrelated families reported with stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS), an autosomal recessive neurodegenerative disorder with onset in the first years of life following normal early development. The disorder is characterised by cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some individuals develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy; Changed publications: 30100084, 30401461 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.225 | ACO2 |
Zornitza Stark changed review comment from: Ataxia is part of the phenotype. Sources: Expert list; to: Ataxia is part of the phenotype, particularly in more mildly affected individuals, where it can be a presenting feature. Episodic ataxia also reported. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.224 | EXOSC5 |
Zornitza Stark gene: EXOSC5 was added gene: EXOSC5 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: EXOSC5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EXOSC5 were set to 32504085; 29302074 Phenotypes for gene: EXOSC5 were set to Short stature; Motor developmental delays; Cerebellar hypoplasia; Ataxia Review for gene: EXOSC5 was set to GREEN Added comment: - PMID: 32504085 (2020) - Five patients from four families with biallelic variants in EXOSC5. Clinical features included short stature (3/5), developmental delays that affect motor skills (3/5), hypotonia (4/5), ataxia (3/4), cerebellar hypoplasia/atrophy (4/5). Cognitive function was generally preserved, but included mild speech delays in one patient. Cerebellar ataxia was described in two sibs and one singleton - all of whom were compound heterozygous for the p.Thr114Ile variant, inherited in trans with a frameshift variant (p.His30Thrfs*35) or deletion involving exons 5–6 of EXOSC5, respectively. A LoF zebrafish model resulted in a variety of morphological defects including shortened and curved tails/bodies, reduced eye/head size and oedema. Functional studies of the variants in budding yeast and cultured cells showed some defects in RNA exosome function and interactions, that could not be explained by decrease in the steady-state level of EXOSC5. - PMID: 29302074 (2019) - Three sibs with a homozygous EXOSC5 variant (p.Thr114Ile), associated with mild motor delays, cerebellar ataxia, nystagmus, dysarthria, and moderate ID. The family is also described in PMID: 30950035. No functional studies of the variant were undertaken. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.220 | HARS |
Bryony Thompson gene: HARS was added gene: HARS was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: HARS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HARS were set to 32296180 Phenotypes for gene: HARS were set to multisystem ataxic syndrome Review for gene: HARS was set to AMBER Added comment: 3 cases from 2 unrelated families with biallelic variants and paediatric onset of progressive ataxic gait as a feature of the condition. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.219 | UBTF |
Bryony Thompson changed review comment from: Ataxia reported as a feature of the condition in 4 unrelated cases with de novo missense variants. Sources: Expert list; to: Paediatric ataxia reported as a feature of the condition in 4 unrelated cases with de novo missense variants. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.218 | UBTF |
Bryony Thompson gene: UBTF was added gene: UBTF was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: UBTF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: UBTF were set to 29300972 Phenotypes for gene: UBTF were set to Neurodegeneration, childhood-onset, with brain atrophy MIM#617672 Review for gene: UBTF was set to GREEN Added comment: Ataxia reported as a feature of the condition in 4 unrelated cases with de novo missense variants. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.216 | MTFMT |
Bryony Thompson gene: MTFMT was added gene: MTFMT was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: MTFMT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MTFMT were set to 26060307; 24461907 Phenotypes for gene: MTFMT were set to Combined oxidative phosphorylation deficiency 15 MIM#614947; Mitochondrial complex I deficiency, nuclear type 27 MIM#618248 Review for gene: MTFMT was set to GREEN Added comment: Five unrelated cases reported with paediatric onset ataxia as a prominent feature of the condition. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.214 | FA2H |
Bryony Thompson gene: FA2H was added gene: FA2H was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: FA2H was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FA2H were set to 31135052 Phenotypes for gene: FA2H were set to Spastic paraplegia 35, autosomal recessive MIM#612319 Review for gene: FA2H was set to GREEN Added comment: Limb ataxia is reported as a feature of the condition in at least 13 cases with mainly paediatric onset. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.212 | CACNA1A | Bryony Thompson Added comment: Comment on list classification: Ataxia can be caused by a triplet repeat expansion in this gene, which is not detectable with current WES/WGS technologies. However, SNVs have also been reported as disease-causing. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.210 | SLC44A1 |
Zornitza Stark gene: SLC44A1 was added gene: SLC44A1 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: SLC44A1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC44A1 were set to 31855247 Phenotypes for gene: SLC44A1 were set to Childhood-onset neurodegeneration; progressive ataxia tremor cognitive decline dysphagia optic atrophy dysarthria Review for gene: SLC44A1 was set to GREEN Added comment: Four affected individuals from three families with homozygous frameshift variants. Functional evidence points to impaired choline transporter function yet unchanged membrane phosphatidylcholine content. Choline treatments may be beneficial. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.182 | XRCC1 |
Bryony Thompson gene: XRCC1 was added gene: XRCC1 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: XRCC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: XRCC1 were set to 28002403; 29472272 Phenotypes for gene: XRCC1 were set to Spinocerebellar ataxia, autosomal recessive 26 MIM#617633 Review for gene: XRCC1 was set to GREEN Added comment: Three South Asian cases (one with early adult onset and the other two with onset in childhood) reported with slowly progressive cerebellar ataxia accompanied by sensorimotor neuropathy. All with the recurrent splice variant (c.1293G>C, 2 homozygotes and a compound heterozygote). Mice with conditional deletion of the Xrcc1 gene in the brain showed cerebellar ataxia. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.181 | RUBCN | Bryony Thompson Added comment: Comment on list classification: Also supporting in vitro functional assays. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.163 | CTBP1 |
Bryony Thompson gene: CTBP1 was added gene: CTBP1 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: CTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CTBP1 were set to 27094857; 28955726; 31041561 Phenotypes for gene: CTBP1 were set to Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome, MIM#617915 Review for gene: CTBP1 was set to GREEN Added comment: Paediatric onset of ataxia and >3 cases reported. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.161 | VRK1 | Bryony Thompson Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.155 | SETX |
Bryony Thompson gene: SETX was added gene: SETX was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: SETX was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SETX were set to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 MIM#606002 Review for gene: SETX was set to GREEN Added comment: Onset usually in mid-teens, average 15 years (range 2 to 20 years). Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.153 | SACS |
Bryony Thompson gene: SACS was added gene: SACS was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: SACS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SACS were set to Spastic ataxia, Charlevoix-Saguenay type MIM#270550 Review for gene: SACS was set to GREEN Added comment: Onset usually in infancy or early childhood. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.151 | RNF216 |
Bryony Thompson gene: RNF216 was added gene: RNF216 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: RNF216 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: RNF216 were set to Cerebellar ataxia and hypogonadotropic hypogonadism MIM#212840 Review for gene: RNF216 was set to GREEN Added comment: Onset of ataxia is variable and can be from early childhood (ORPHA:1173). Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.149 | PRRT2 |
Bryony Thompson gene: PRRT2 was added gene: PRRT2 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: PRRT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: PRRT2 were set to 26598494; 31193310; 30501978; 30713971 Phenotypes for gene: PRRT2 were set to Episodic kinesigenic dyskinesia 1 MIM#128200; Convulsions, familial infantile, with paroxysmal choreoathetosis MIM#602066; Seizures, benign familial infantile, 2 MIM#605751 Review for gene: PRRT2 was set to GREEN Added comment: Ataxia can be a prominent feature of the condition, particularly in biallelic cases. Onset of ataxia is variable, from paediatric to adult. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.146 | POLG |
Bryony Thompson gene: POLG was added gene: POLG was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: POLG was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4A (Alpers type) MIM#203700; Mitochondrial DNA depletion syndrome 4B (MNGIE type) MIM#613662; Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE) MIM#607459; Progressive external ophthalmoplegia, autosomal recessive 1 MIM#258450 Review for gene: POLG was set to GREEN Added comment: Variable age of onset, including infancy and early childhood. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.144 | PNPLA6 |
Bryony Thompson gene: PNPLA6 was added gene: PNPLA6 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: PNPLA6 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PNPLA6 were set to Boucher-Neuhauser syndrome MIM#215470; Laurence-Moon syndrome MIM#245800; Oliver-McFarlane syndrome MIM#275400; Spastic paraplegia 39, autosomal recessive MIM#612020 Review for gene: PNPLA6 was set to GREEN Added comment: Variable age of onset for neurological features (including ataxia) from childhood to adulthood. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.139 | SPTBN2 |
Zornitza Stark gene: SPTBN2 was added gene: SPTBN2 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: SPTBN2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SPTBN2 were set to 23236289; 23838597; 22781464; 31617442; 31066025 Phenotypes for gene: SPTBN2 were set to Spinocerebellar ataxia, autosomal recessive 14, MIM# 615386; Spinocerebellar ataxia 5, MIM# 600224 Review for gene: SPTBN2 was set to GREEN Added comment: Both mono-allelic and bi-allelic variants in this gene are associated with childhood-onset ataxia. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.133 | STUB1 |
Zornitza Stark gene: STUB1 was added gene: STUB1 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: STUB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: STUB1 were set to 25258038; 24742043 Phenotypes for gene: STUB1 were set to Spinocerebellar ataxia, autosomal recessive 16, MIM# 615768 Review for gene: STUB1 was set to GREEN Added comment: Onset is typically in adolescence but onset in childhood also reported. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.131 | MSTO1 |
Bryony Thompson gene: MSTO1 was added gene: MSTO1 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: MSTO1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Phenotypes for gene: MSTO1 were set to Myopathy, mitochondrial, and ataxia MIM#617675 Review for gene: MSTO1 was set to GREEN Added comment: Onset usually in early childhood. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.129 | MARS2 |
Bryony Thompson gene: MARS2 was added gene: MARS2 was added to Ataxia - paediatric. Sources: Expert list SV/CNV tags were added to gene: MARS2. Mode of inheritance for gene: MARS2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MARS2 were set to Spastic ataxia 3, autosomal recessive MIM#611390 Review for gene: MARS2 was set to GREEN Added comment: Variable age at onset (range 2 to 59 years, mean 24 years). Complex duplication rearrangements the only cause reported to date. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.127 | SYNE1 |
Zornitza Stark gene: SYNE1 was added gene: SYNE1 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: SYNE1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SYNE1 were set to 23325900; 27086870 Phenotypes for gene: SYNE1 were set to Spinocerebellar ataxia, autosomal recessive 8, MIM# 610743 Review for gene: SYNE1 was set to GREEN Added comment: Typical onset is in adulthood, but childhood-onset cases reported. Intra-familial variability. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.125 | KIF1C |
Bryony Thompson gene: KIF1C was added gene: KIF1C was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: KIF1C was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: KIF1C were set to Spastic ataxia 2, autosomal recessive MIM#611302 Review for gene: KIF1C was set to GREEN Added comment: Onset usually in adolescence. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.122 | KCNC3 |
Bryony Thompson gene: KCNC3 was added gene: KCNC3 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: KCNC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: KCNC3 were set to Spinocerebellar ataxia 13 MIM#605259 Review for gene: KCNC3 was set to GREEN Added comment: Variable age at onset, ranging from childhood to late adulthood. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.119 | ITPR1 |
Bryony Thompson gene: ITPR1 was added gene: ITPR1 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: ITPR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: ITPR1 were set to Spinocerebellar ataxia 15 MIM#606658; Spinocerebellar ataxia 29, congenital nonprogressive MIM#117360 Review for gene: ITPR1 was set to GREEN Added comment: Wide range of onset from birth to adulthood. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.117 | FXN |
Bryony Thompson gene: FXN was added gene: FXN was added to Ataxia - paediatric. Sources: Expert list STR tags were added to gene: FXN. Mode of inheritance for gene: FXN was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FXN were set to Friedreich ataxia MIM#229300 Review for gene: FXN was set to GREEN Added comment: Onset usually before adolescence. Most common genetic abnormality is the trinucleotide repeat expansion, but also SNVs and indels reported. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.115 | TCTN1 | Zornitza Stark changed review comment from: Rare cause of JBS, ataxia not specifically mentioned.; to: Rare cause of JBS, ataxia specifically mentioned in at least one individual. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.113 | FLVCR1 |
Bryony Thompson gene: FLVCR1 was added gene: FLVCR1 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: FLVCR1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FLVCR1 were set to Ataxia, posterior column, with retinitis pigmentosa MIM#609033 Review for gene: FLVCR1 was set to GREEN Added comment: Onset usually in childhood. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.111 | FGF14 |
Bryony Thompson gene: FGF14 was added gene: FGF14 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: FGF14 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: FGF14 were set to Spinocerebellar ataxia 27 MIM#609307 Review for gene: FGF14 was set to GREEN Added comment: Onset in late-childhood to early adulthood (12 to 20 years). Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.105 | EIF2B5 |
Bryony Thompson gene: EIF2B5 was added gene: EIF2B5 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: EIF2B5 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: EIF2B5 were set to Leukoencephalopathy with vanishing white matter MIM#603896 Review for gene: EIF2B5 was set to GREEN Added comment: Ataxia is a prominent feature of the condition and onset usually in late infancy or childhood (1 to 6 years). Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.103 | EIF2B4 |
Bryony Thompson gene: EIF2B4 was added gene: EIF2B4 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: EIF2B4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: EIF2B4 were set to Leukoencephalopathy with vanishing white matter MIM#603896 Review for gene: EIF2B4 was set to GREEN Added comment: Ataxia is a prominent feature of the condition and onset usually in late infancy or childhood (1 to 6 years). Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.99 | EIF2B3 |
Bryony Thompson gene: EIF2B3 was added gene: EIF2B3 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: EIF2B3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: EIF2B3 were set to Leukoencephalopathy with vanishing white matter MIM#603896 Review for gene: EIF2B3 was set to GREEN Added comment: Ataxia is a prominent feature of the condition and onset usually in late infancy or childhood (1 to 6 years). Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.97 | EIF2B2 |
Bryony Thompson gene: EIF2B2 was added gene: EIF2B2 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: EIF2B2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: EIF2B2 were set to Leukoencephalopathy with vanishing white matter MIM#603896 Review for gene: EIF2B2 was set to GREEN Added comment: Ataxia is a prominent feature of the condition and onset usually in late infancy or childhood (1 to 6 years). Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.95 | EIF2B1 |
Bryony Thompson gene: EIF2B1 was added gene: EIF2B1 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: EIF2B1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: EIF2B1 were set to Leukoencephalopathy with vanishing white matter MIM#603896 Review for gene: EIF2B1 was set to GREEN Added comment: Ataxia is a prominent feature of the condition and onset usually in late infancy or childhood (1 to 6 years). Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.93 | COA7 |
Bryony Thompson gene: COA7 was added gene: COA7 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: COA7 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: COA7 were set to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MIM#618387 Review for gene: COA7 was set to GREEN Added comment: Onset usually in the first decade. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.91 | CACNA1G |
Bryony Thompson gene: CACNA1G was added gene: CACNA1G was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: CACNA1G was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: CACNA1G were set to Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits MIM#618087 Review for gene: CACNA1G was set to GREEN Added comment: Onset of ataxia is soon after birth or in early infancy. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.89 | CACNA1A |
Bryony Thompson gene: CACNA1A was added gene: CACNA1A was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: CACNA1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: CACNA1A were set to Episodic ataxia, type 2 MIM#108500 Review for gene: CACNA1A was set to GREEN Added comment: Onset of episodic ataxia usually in childhood or adolescence. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.85 | ATP1A3 |
Bryony Thompson gene: ATP1A3 was added gene: ATP1A3 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: ATP1A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: ATP1A3 were set to Alternating hemiplegia of childhood 2 MIM#614820; CAPOS syndrome MIM#601338 Review for gene: ATP1A3 was set to GREEN Added comment: Onset of ataxia is usually in infancy or childhood. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.81 | ATM |
Bryony Thompson gene: ATM was added gene: ATM was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: ATM was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ATM were set to Ataxia-telangiectasia MIM#208900 Review for gene: ATM was set to GREEN Added comment: Onset of ataxia is usually in childhood. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.79 | ANO10 |
Bryony Thompson gene: ANO10 was added gene: ANO10 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: ANO10 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ANO10 were set to Spinocerebellar ataxia, autosomal recessive 10 MIM#613728 Review for gene: ANO10 was set to GREEN Added comment: Onset of ataxia is in adolescence or adulthood. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.66 | TMEM240 |
Zornitza Stark gene: TMEM240 was added gene: TMEM240 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: TMEM240 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TMEM240 were set to 25070513 Phenotypes for gene: TMEM240 were set to Spinocerebellar ataxia 21, MIM# 607454 Review for gene: TMEM240 was set to GREEN Added comment: At least 8 unrelated families reported. Onset in the first decades of life, including in childhood, of slowly progressive cerebellar ataxia, which is associated with cognitive impairment in most patients Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.64 | AFG3L2 |
Bryony Thompson gene: AFG3L2 was added gene: AFG3L2 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: AFG3L2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: AFG3L2 were set to 20725928 Phenotypes for gene: AFG3L2 were set to Spastic ataxia 5, autosomal recessive MIM#614487; Spinocerebellar ataxia 28 MIM#610246 Review for gene: AFG3L2 was set to GREEN Added comment: The onset of the recessive form of ataxia is usually in infancy or childhood. The dominantly inherited form of ataxia is mostly adult onset, but onset in childhood has been reported. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.62 | TTPA |
Zornitza Stark gene: TTPA was added gene: TTPA was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: TTPA was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TTPA were set to Ataxia with isolated vitamin E deficiency, MIM# 277460 Review for gene: TTPA was set to GREEN Added comment: Ataxia secondary to vitamin E deficiency. Variable age of onset, but paediatric cases reported. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.59 | VPS13D |
Zornitza Stark gene: VPS13D was added gene: VPS13D was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: VPS13D was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: VPS13D were set to 29604224; 29518281 Phenotypes for gene: VPS13D were set to Spinocerebellar ataxia, autosomal recessive 4, MIM# 607317 Review for gene: VPS13D was set to GREEN Added comment: Seven unrelated families reported, some functional data. Age at onset is highly variable: some have onset in early childhood with delayed walking, whereas others have onset of gait difficulties in adulthood. Additional features may include dysarthria, oculomotor abnormalities, distal sensory impairment, dystonia, chorea, hypotonia, pyramidal signs, and cerebellar atrophy on brain imaging. The disorder is slowly progressive. Some individuals with onset in childhood may have global developmental delay with mild intellectual disability. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.55 | ABHD12 |
Bryony Thompson gene: ABHD12 was added gene: ABHD12 was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: ABHD12 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ABHD12 were set to Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract MIM#612674 Review for gene: ABHD12 was set to GREEN Added comment: Ataxia is a prominent feature of the condition and onset is usually in childhood or adolescence. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.53 | AAAS |
Bryony Thompson gene: AAAS was added gene: AAAS was added to Ataxia - paediatric. Sources: Expert list Mode of inheritance for gene: AAAS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: AAAS were set to Achalasia-addisonianism-alacrimia syndrome MIM#231550 Review for gene: AAAS was set to GREEN Added comment: Ataxia is a feature of the condition and onset is usually in childhood. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.50 | PITRM1 |
Bryony Thompson gene: PITRM1 was added gene: PITRM1 was added to Ataxia - paediatric. Sources: Literature Mode of inheritance for gene: PITRM1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PITRM1 were set to 26697887; 29764912 Phenotypes for gene: PITRM1 were set to Cerebellar atrophy; mental retardation; spinocerebellar ataxia; cognitive decline; psychosis Review for gene: PITRM1 was set to GREEN Added comment: Three families with two unique variants and in vitro functional assays. Cases and mouse model have spinocerebellar ataxia as a prominent feature of the phenotype. No OMIM phenotype. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.47 | ACBD5 |
Bryony Thompson changed review comment from: 2 unrelated families and no functional evidence Sources: Expert list; to: 2 unrelated families and no functional evidence linking the gene to an ataxia phenotype Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.47 | WDPCP |
Bryony Thompson gene: WDPCP was added gene: WDPCP was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: WDPCP was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: WDPCP were set to ?Bardet-Biedl syndrome 15, 615992; ?Congenital heart defects, hamartomas of tongue, and polysyndactyly, 217085 Review for gene: WDPCP was set to RED Added comment: Ataxia not a reported phenotypic feature associated with this gene.` Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.46 | VRK1 |
Bryony Thompson gene: VRK1 was added gene: VRK1 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: VRK1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: VRK1 were set to Pontocerebellar hypoplasia type 1A, 607596 Review for gene: VRK1 was set to RED Added comment: Ataxia can be a feature of the phenotype. Biallelic variants cause pontocerebellar hypoplasia and death before age 12, thus not a relevant gene for testing in an adult hospital. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.45 | TTI1 |
Bryony Thompson gene: TTI1 was added gene: TTI1 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: TTI1 was set to Unknown Review for gene: TTI1 was set to RED Added comment: No reported association with ataxia. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.44 | TTC8 |
Bryony Thompson gene: TTC8 was added gene: TTC8 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: TTC8 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TTC8 were set to Bardet-Biedl syndrome 8, 615985 Review for gene: TTC8 was set to RED Added comment: Ataxia is not a reported feature of this subtype of BBS Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.43 | TSEN34 |
Bryony Thompson gene: TSEN34 was added gene: TSEN34 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: TSEN34 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TSEN34 were set to ?Pontocerebellar hypoplasia type 2C, 612390 Review for gene: TSEN34 was set to RED Added comment: No publications associated with ataxia, and ataxia is not a prominent feature of the condition. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.42 | TSEN2 |
Bryony Thompson gene: TSEN2 was added gene: TSEN2 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: TSEN2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TSEN2 were set to Pontocerebellar hypoplasia type 2B, 612389 Review for gene: TSEN2 was set to RED Added comment: Ataxia is not a prominent feature of this phenotype. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.41 | TRIM32 |
Bryony Thompson gene: TRIM32 was added gene: TRIM32 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: TRIM32 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TRIM32 were set to Muscular dystrophy, limb-girdle, autosomal recessive 8, 254110; ?Bardet-Biedl syndrome 11, 615988 Review for gene: TRIM32 was set to RED Added comment: Ataxia is not a reported feature associated with this gene. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.39 | SVBP |
Bryony Thompson gene: SVBP was added gene: SVBP was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: SVBP was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SVBP were set to Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly, 618569 Review for gene: SVBP was set to GREEN Added comment: Ataxia is a prominent feature of the phenotype for this condition. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.37 | SNAP25 |
Bryony Thompson gene: SNAP25 was added gene: SNAP25 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: SNAP25 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SNAP25 were set to 29491473; 25381298; 17283335 Phenotypes for gene: SNAP25 were set to ?Myasthenic syndrome, congenital, 18, 616330; cerebellar ataxia and seizures Review for gene: SNAP25 was set to GREEN Added comment: Phenotype in 3 reported cases and mouse model includes ataxia as a feature. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.36 | SAR1B |
Bryony Thompson gene: SAR1B was added gene: SAR1B was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: SAR1B was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SAR1B were set to Chylomicron retention disease, 246700 Review for gene: SAR1B was set to RED Added comment: Ataxia is not a reported prominent feature of the condition. Neurological symptoms are secondary to malabsorption. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.35 | RARS2 |
Bryony Thompson gene: RARS2 was added gene: RARS2 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: RARS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RARS2 were set to 31429931 Phenotypes for gene: RARS2 were set to Pontocerebellar hypoplasia, type 6, 611523; early onset cerebellar ataxia Review for gene: RARS2 was set to RED Added comment: Ataxia is not a prominent feature of PCH. A homozygous putative pathogenic variant has been identified in one family with early onset cerebellar ataxia. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.31 | PNKD |
Bryony Thompson gene: PNKD was added gene: PNKD was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: PNKD was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: PNKD were set to Paroxysmal nonkinesigenic dyskinesia 1, 118800 Review for gene: PNKD was set to GREEN Added comment: Condition has many overlapping features with episodic ataxia. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.30 | PCYT2 |
Bryony Thompson gene: PCYT2 was added gene: PCYT2 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: PCYT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PCYT2 were set to 31637422 Phenotypes for gene: PCYT2 were set to global developmental delay; regression; spastic parapesis or tetraparesis; epilepsy; progressive cerebral and cerebellar atrophy Review for gene: PCYT2 was set to RED Added comment: Ataxia is not a prominent feature of the condition. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.28 | MKKS |
Bryony Thompson gene: MKKS was added gene: MKKS was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: MKKS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MKKS were set to 15637713 Phenotypes for gene: MKKS were set to Bardet-Biedl syndrome 6, 605231 Review for gene: MKKS was set to AMBER Added comment: Ataxia is not reported as a prominent feature of the phenotype. However, ataxia has been reported in at least 1 case with BBS6. There were four BBS6 cases reported in the publication, and 18/21 BBS cases had ataxia, therefore it is unknown if all 4 cases had ataxia. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.27 | EXOSC3 |
Bryony Thompson changed review comment from: Ataxia is not a prominent feature of the phenotype Sources: Expert list; to: Ataxia is not a prominent feature of the phenotype Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.27 | EXOSC3 |
Bryony Thompson gene: EXOSC3 was added gene: EXOSC3 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: EXOSC3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: EXOSC3 were set to Pontocerebellar hypoplasia, type 1B, 614678 Added comment: Ataxia is not a prominent feature of the phenotype Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.26 | ELOVL1 |
Bryony Thompson gene: ELOVL1 was added gene: ELOVL1 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: ELOVL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: ELOVL1 were set to Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, 618527 Review for gene: ELOVL1 was set to RED Added comment: Ataxia is not a prominent feature of this condition. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.25 | CYP2U1 |
Bryony Thompson gene: CYP2U1 was added gene: CYP2U1 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: CYP2U1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CYP2U1 were set to Spastic paraplegia 56, autosomal recessive, 615030 Added comment: Ataxia is not a prominent feature of the phenotype Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.24 | COQ5 |
Bryony Thompson gene: COQ5 was added gene: COQ5 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: COQ5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COQ5 were set to 29044765 Phenotypes for gene: COQ5 were set to Cerebellar ataxia; encephalopathy; generalized tonic-clonic seizures; intellectual disability Review for gene: COQ5 was set to RED Added comment: Only one reported family, without functional assays linking the gene to ataxia. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.23 | CHMP1A |
Bryony Thompson gene: CHMP1A was added gene: CHMP1A was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: CHMP1A was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CHMP1A were set to Pontocerebellar hypoplasia, type 8, 614961 Review for gene: CHMP1A was set to RED Added comment: Ataxia is not a prominent feature of the phenotype. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.22 | CCDC28B |
Bryony Thompson gene: CCDC28B was added gene: CCDC28B was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: CCDC28B was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CCDC28B were set to {Bardet-Biedl syndrome 1, modifier of}, 209900 Review for gene: CCDC28B was set to RED Added comment: Modifier of BBS Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.21 | BBS9 |
Bryony Thompson gene: BBS9 was added gene: BBS9 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: BBS9 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: BBS9 were set to Bardet-Biedl syndrome 9, 615986 Review for gene: BBS9 was set to RED Added comment: Ataxia is not a reported feature of the phenotype for this subtype of BBS. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.20 | BBS7 |
Bryony Thompson gene: BBS7 was added gene: BBS7 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: BBS7 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: BBS7 were set to Bardet-Biedl syndrome 7, 615984 Review for gene: BBS7 was set to RED Added comment: Ataxia is not a reported feature of the phenotype of this subtype of BBS. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.19 | BBS5 |
Bryony Thompson gene: BBS5 was added gene: BBS5 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: BBS5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BBS5 were set to 15637713 Phenotypes for gene: BBS5 were set to Bardet-Biedl syndrome 5, 615983 Review for gene: BBS5 was set to RED Added comment: Ataxia is not a common feature reported with this subtype of BBS. One family with linkage to BBS5 (not sequenced) has been reported with ataxia. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.18 | BBS4 |
Bryony Thompson gene: BBS4 was added gene: BBS4 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: BBS4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: BBS4 were set to Bardet-Biedl syndrome 4, 615982 Review for gene: BBS4 was set to RED Added comment: Ataxia is not a reported feature of the phenotype of this subtype of BBS. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.17 | BBS2 |
Bryony Thompson gene: BBS2 was added gene: BBS2 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: BBS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BBS2 were set to 15637713 Phenotypes for gene: BBS2 were set to Bardet-Biedl syndrome 2, 615981 Review for gene: BBS2 was set to RED Added comment: Ataxia is not a reported common feature of this subtype of BBS. Ataxia may be present in one family with BBS2, but not stated outright in the publication (18/21 families had ataxia and there was only one BBS2 family). Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.16 | BBS12 |
Bryony Thompson gene: BBS12 was added gene: BBS12 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: BBS12 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: BBS12 were set to Bardet-Biedl syndrome 12, 615989 Added comment: Ataxia is not a reported feature of the phenotype. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.15 | BBS10 |
Bryony Thompson gene: BBS10 was added gene: BBS10 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: BBS10 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: BBS10 were set to Bardet-Biedl syndrome 10, 615987 Review for gene: BBS10 was set to RED Added comment: Ataxia is not a reported feature of condition. Only reported as a common feature of BBS1. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.14 | ARL6 |
Bryony Thompson gene: ARL6 was added gene: ARL6 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: ARL6 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ARL6 were set to Bardet-Biedl syndrome 3, 600151 Review for gene: ARL6 was set to RED Added comment: Ataxia is not a reported feature of condition. Only reported as a common feature of BBS1. Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.13 | AMPD2 |
Bryony Thompson gene: AMPD2 was added gene: AMPD2 was added to Ataxia - paediatric_RMH. Sources: Other Mode of inheritance for gene: AMPD2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: AMPD2 were set to Pontocerebellar hypoplasia, type 9, 615809 Review for gene: AMPD2 was set to RED Added comment: Ataxia is not a reported feature of this condition. Sources: Other |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.11 | BBS1 |
Bryony Thompson gene: BBS1 was added gene: BBS1 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: BBS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BBS1 were set to 15637713 Phenotypes for gene: BBS1 were set to Bardet-Biedl syndrome 1, 209900 Review for gene: BBS1 was set to GREEN Added comment: Ataxia is a common feature of the phenotype Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.7 | DOCK3 |
Bryony Thompson gene: DOCK3 was added gene: DOCK3 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: DOCK3 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DOCK3 were set to Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia, MIM#618292 Review for gene: DOCK3 was set to GREEN Added comment: Ataxia is a feature of the phenotype Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.4 | AP1S2 |
Bryony Thompson gene: AP1S2 was added gene: AP1S2 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: AP1S2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: AP1S2 were set to Mental retardation, X-linked syndromic 5, MIM#304340 Review for gene: AP1S2 was set to GREEN Added comment: Ataxia is part of the phenotype Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v0.1 | ACBD5 |
Bryony Thompson gene: ACBD5 was added gene: ACBD5 was added to Ataxia - paediatric_RMH. Sources: Expert list Mode of inheritance for gene: ACBD5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACBD5 were set to 27799409; 23105016 Phenotypes for gene: ACBD5 were set to Leukodystrophy; syndromic cleft palate; ataxia; retinal dystrophy Review for gene: ACBD5 was set to AMBER Added comment: 2 unrelated families and no functional evidence Sources: Expert list |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||