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| 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 |
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| 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 |
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| Ataxia v2.60 | GAN | Bryony Thompson Marked gene: GAN as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.60 | GAN | Bryony Thompson Gene: gan has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.60 | GAN | Bryony Thompson Classified gene: GAN as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia v2.60 | GAN | Bryony Thompson Gene: gan has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| Ataxia v0.0 | HEXA |
Bryony Thompson gene: HEXA was added gene: HEXA was added to Ataxia - paediatric_RMH. Sources: Expert Review Green,Royal Melbourne Hospital Mode of inheritance for gene: HEXA was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: HEXA were set to GM2-gangliosidosis, several forms, 272800; Tay-Sachs disease, 272800 |
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