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| Mendeliome v1.3227 | MT-TY |
Zornitza Stark gene: MT-TY was added gene: MT-TY was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-TY. Mode of inheritance for gene gene: MT-TY was set to MITOCHONDRIAL Publications for gene: MT-TY were set to 11071502; 11756614; 11594340; 33279411; 30643656; 32684384; 32485333; 33279411 Phenotypes for gene: MT-TY were set to Mitochondrial disease (MONDO:0044970), MT-TY-related Review for gene: MT-TY was set to GREEN Added comment: DEFINITIVE by ClinGen. Multiple individuals reported. Age of onset in affected individuals is variable and clinical features seen include myopathy with or without ophthalmoplegia. There is at least one case report with a more severe phenotype with neuropathy, ataxia, seizures, myoclonus, sensorineural hearing loss, and pigmentary retinopathy. Muscle biopsy in affected individuals has shown COX-negative and ragged red fibers, with variable mitochondrial respiratory chain enzyme deficiencies. The variants in affected individuals are often present at highest heteroplasmy levels in muscle and may be undetectable in other tissues such as blood and buccal tissue. Multiple single fiber studies were performed in these patients and supportive of variant pathogenicity Sources: Expert list |
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| Mendeliome v1.3219 | MT-TS2 |
Zornitza Stark gene: MT-TS2 was added gene: MT-TS2 was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-TS2. Mode of inheritance for gene gene: MT-TS2 was set to MITOCHONDRIAL Publications for gene: MT-TS2 were set to 9792552; 10090882; 16950817; 21257182; 22369973; 22378285 Phenotypes for gene: MT-TS2 were set to Mitochondrial disease (MONDO:0044970), MT-TS2-related Review for gene: MT-TS2 was set to GREEN Added comment: MODERATE by ClinGen. At least 7 individuals reported. Affected individuals had varying clinical features including cataracts, retinal dystrophy, hearing loss, myopathy, ataxia, seizures, global developmental delay, diabetes, Wolff-Parkinson-White arrhythmia, hypertrophic cardiomyopathy, and hypogonadotropic hypogonadism. Lab investigations revealed elevated blood lactate and elevated creatine kinase. Muscle biopsy, when performed, generally showed reduced activities of complexes I, I+III, III, and/or IV. Brain imaging was normal in some cases. In one individual brain imaging revealed changes in the basal ganglia and diffuse atrophy with an enlarged cisterna magna and in another showed changes in the cerebral white matter. Heteroplasmy levels were variable – some individuals had the highest levels in muscle with the variant being undetectable in other tissues while others had the variant present at homoplasmy in multiple tissues. Northern blotting and single fiber testing further supported variant pathogenicity. Sources: Expert list |
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| Mendeliome v1.3196 | MT-TH |
Zornitza Stark gene: MT-TH was added gene: MT-TH was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-TH. Mode of inheritance for gene gene: MT-TH was set to MITOCHONDRIAL Publications for gene: MT-TH were set to 12682337; 14967777; 15111688; 21704194; 21931169; 23696415; 35092007; 24920829; 21704194 Phenotypes for gene: MT-TH were set to Mitochondrial disease (MONDO:0044970), MT-TH-related Review for gene: MT-TH was set to GREEN Added comment: DEFINITIVE by ClinGen. More than 5 individuals reported. Age of onset in affected individuals varied from adolescence to the 40s. Clinical features included stroke-like episodes, seizures, myoclonus, ataxia, optic atrophy, retinal dystrophy, cataracts, hearing loss, hypogonadism, and mood disorder. Cerebellar vermis hypoplasia and signal changes in the basal ganglia, dentate nuclei, temporal lobes, and occipital lobes were seen on brain imaging. Tissue biopsies identified ragged red fibers and COX-negative fibers. Laboratory investigations showed increased blood and cerebrospinal fluid lactate. Decreased activities of complexes I and IV were variably seen in muscle. Heteroplasmy levels of the variants in affected individuals ranged from 81% to homoplasmic in muscle, 33-87% in urine, 1-60% in blood, and undetectable to homoplasmic in fibroblasts. Single fiber testing, cybrid analysis, and Northern blot analysis further supported variant pathogenicity. This gene-disease relationship is also supported by known biochemical function and functional alteration in patient and non-patient cells (in vitro functional assays demonstrated reduced rates of mitochondrial translation as a result of variants in MT-TH; PMID: 24920829, 21704194). Sources: Expert list |
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| Mendeliome v1.3194 | MT-TG |
Zornitza Stark gene: MT-TG was added gene: MT-TG was added to Mendeliome. Sources: Expert list Mode of inheritance for gene gene: MT-TG was set to MITOCHONDRIAL Publications for gene: MT-TG were set to 8079988; 9199564; 11971101; 16120360; 32337339; 35432167; 10090480 Phenotypes for gene: MT-TG were set to Mitochondrial disease (MONDO:0044970), MT-TG-related Review for gene: MT-TG was set to GREEN Added comment: MODERATE by ClinGen. Four variants reported in at least 6 individuals. Age of onset in affected individuals varied from early in life to the 20s. Clinical features included hypertrophic cardiomyopathy, myopathy, peripheral neuropathy, exercise intolerance, headache, seizures, ataxia, dystonic posturing, optic atrophy, retinal dystrophy, cataracts, and hearing loss. Progressive atrophy and bilateral basal ganglia calcifications were seen on brain imaging. Tissue biopsies identified ragged red fibers and decreased COX histochemical activity in muscle. Lab values showed increased blood lactate and increased creatine kinase. Decreased activities of complexes I, III, and IV were observed in biopsied muscle. Heteroplasmy levels of the variants in affected individuals ranged from 88-92% in muscle, 40-56% in urine, undetectable to 32% in blood, 27% in buccal samples, and was undetectable when assessed in fibroblasts. Single fiber testing and cybrid analysis further supported variant pathogenicity. This gene-disease relationship is also supported by known biochemical function and functional alterations in patient cells (in vitro functional assays demonstrated reduced rates of mitochondrial translation as a result of variants in MT-TG; PMID: 10090480). Sources: Expert list |
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| Mendeliome v1.3187 | MT-TD |
Zornitza Stark gene: MT-TD was added gene: MT-TD was added to Mendeliome. Sources: Expert list Mode of inheritance for gene gene: MT-TD was set to MITOCHONDRIAL Publications for gene: MT-TD were set to 9811342; 10488907; 16059939; 18676632; 23696415; 25447692; 27536005; 30030363; 3054486; 19535463 Phenotypes for gene: MT-TD were set to Mitochondrial disease (MONDO:0044970), MT-TD-related Review for gene: MT-TD was set to GREEN Added comment: MODERATE by ClinGen. At least 3 variants reported in unrelated individuals. These variants were generally present at high levels of heteroplasmy in muscle tissue and at lower to undetectable levels in other tissues such as blood, saliva, buccal tissue, urine, and fibroblasts, highlighting the diagnostic importance of muscle biopsy in MT-TD-related primary mitochondrial disease. Single fiber studies were performed in several individuals with results supporting variant pathogenicity. This gene-disease association is also supported by functional implication given protein interaction with the multitude of other mitochondrial translation proteins linked to primary mitochondrial disease (PMID: 30030363 ). Respiratory deficient yeast strains due to a single variant in MT-TD have been created and compelling rescue studies have been performed (PMIDs: 7024270, 3054486). E. coli carrying the m.7526A>G variant were also shown to have significantly decreased aminoacylation rates (PMID: 19535463). Sources: Expert list |
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| Mendeliome v1.3179 | MT-ND6 |
Zornitza Stark gene: MT-ND6 was added gene: MT-ND6 was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-ND6. Mode of inheritance for gene gene: MT-ND6 was set to MITOCHONDRIAL Publications for gene: MT-ND6 were set to 5576045; 20019223; 21196529; 10894222; 14684687; 17535832; 19103152; 21749722; 23813926; 25356405; 14595656; 19062322; 11133798; 30741831; 21364701; 2018041 Phenotypes for gene: MT-ND6 were set to Mitochondrial disease (MONDO:0044970), MT-ND6-related Review for gene: MT-ND6 was set to GREEN Added comment: DEFINITIVE by ClinGen. More than 20 affected individuals reported, the m.14484T>C and m.14487T>C variants are recurrent. Affected individuals present with a broad phenotypic spectrum of disease including Leber Hereditary Optic Neuropathy (LHON), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and LSS phenotypes, as well as migraines, tremor, multiple sclerosis, and cardiac involvement. The age of onset is also highly variable, ranging from infantile to adult. Muscle biopsies revealed isolated complex I deficiency, and complex I and III deficiencies; and complex I deficiency was also seen in fibroblasts and liver. Metabolic screening investigations showed elevated lactate and pyruvate in cerebrospinal fluid (CSF) and blood. Heteroplasmy levels in affected individuals ranged from 50% to >95% in skeletal muscle; 25% to >95% in blood, 76% to >95% in fibroblasts, and 65% to >95% in liver; and ranged in healthy family members from undetectable to 92% in blood, undetectable to 95% in urine, 14% to 95% in hair follicles, 16% to 68% in buccal, and was undetectable in muscle in healthy family members. Sources: Expert list |
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| Mendeliome v1.3177 | MT-ND5 |
Zornitza Stark gene: MT-ND5 was added gene: MT-ND5 was added to Mendeliome. Sources: Expert list mtDNA tags were added to gene: MT-ND5. Mode of inheritance for gene gene: MT-ND5 was set to MITOCHONDRIAL Publications for gene: MT-ND5 were set to 17400793; 11938446; 12624137; 18495510; 23918514; 17535832; 29506874; 23034978; 16816025; 9299505; 18977334 Phenotypes for gene: MT-ND5 were set to Mitochondrial disease (MONDO:0044970), MT-ND5-related Review for gene: MT-ND5 was set to GREEN Added comment: DEFINITIVE by ClinGen. More than 20 individuals reported. Two variants are recurrent (m.13513G>A and m.13094T>C). Affected individuals present with a broad phenotypic spectrum of disease including Leber Hereditary Optic Neuropathy (LHON); mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); LSS; myoclonus epilepsy, ragged red fibers (MERRF); and cardiomyopathy. The age of onset is also highly variable, ranging from infantile to adult. Muscle biopsies variably revealed ragged red fibers, isolated complex I deficiency, and variable combined deficiencies of complexes I, III, and/or IV. Metabolic screening investigations showed elevated lactate in cerebrospinal fluid (CSF) and blood and urinary excretion of Krebs cycle intermediates. Heteroplasmy levels in affected individuals ranged from 28% - 90% in skeletal muscle, 23% to 77% in blood, undetectable to 90% in fibroblasts, 51% - 81% in urine; and ranged in healthy family members from undetectable to 20% in blood, undetectable to 25% to 95% in hair follicles, undetectable to 4-6% muscle, and ranged from 27%-45% in other tissues such as urine and buccal samples in healthy family members. Sources: Expert list |
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| Mendeliome v1.3169 | MT-ND2 |
Zornitza Stark gene: MT-ND2 was added gene: MT-ND2 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene gene: MT-ND2 was set to MITOCHONDRIAL Publications for gene: MT-ND2 were set to 26258512; 16738010; 15781840; 12192017 Phenotypes for gene: MT-ND2 were set to Mitochondrial disease (MONDO:0044970), MT-ND2-related Review for gene: MT-ND2 was set to GREEN Added comment: MODERATE by ClinGen. Multiple individuals reported. Age of onset in affected individuals ranged from 9 months old to childhood. Clinical features in affected individuals included Leigh syndrome spectrum, myopathy, ophthalmoplegia, and ptosis. Muscle biopsies revealed ragged red fibers and complex I deficiency. Metabolic screening labs showed elevated lactate and creatine kinase (CK). Heteroplasmy levels were >95% in blood, fibroblasts, and muscle in the individual with Leigh syndrome spectrum. However in the other two individuals with predominantly myopathic features, the variant was present at >94% in muscle and undetectable in other tissues tested. Sources: Expert list |
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| Mendeliome v1.2775 | TACC3 |
Zornitza Stark gene: TACC3 was added gene: TACC3 was added to Mendeliome. Sources: Expert list Mode of inheritance for gene: TACC3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TACC3 were set to 36395215 Phenotypes for gene: TACC3 were set to Female infertility due to oocyte meiotic arrest, MONDO:0044626 Review for gene: TACC3 was set to AMBER Added comment: PMID: 36395215- compound heterozygous variants (Patient 1- p.Ser177Thr/p.Pro395Arg, Patient 2- p.Lys225_Cys236del/p.Gly631Val) in two unrelated females presented with oocyte maturation arrest and undetectable spindles on both polarization and fluorescence microscopy. Their oocytes lacked huoMTOCs and had poorly organized microtubules, similar to the phenotype of TACC3 depletion in vitro, which suggests a loss-of-function mechanism causing oocyte maturation arrest and infertility. Sources: Expert list |
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| Mendeliome v1.2230 | MRUPAV_PLIN4 |
Bryony Thompson STR: MRUPAV_PLIN4 was added STR: MRUPAV_PLIN4 was added to Mendeliome. Sources: Literature STR tags were added to STR: MRUPAV_PLIN4. Mode of inheritance for STR: MRUPAV_PLIN4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: MRUPAV_PLIN4 were set to 32451610; 37145156; 36151849; 35499779 Phenotypes for STR: MRUPAV_PLIN4 were set to myopathy, distal, with rimmed vacuoles MONDO:0014945 Review for STR: MRUPAV_PLIN4 was set to GREEN STR: MRUPAV_PLIN4 was marked as clinically relevant Added comment: Expansion of 33-mer (33 amino acids, 99 bp) identified in coding exon 3 (exon 5) of PLIN4 via linkage analysis and long read sequencing in a large Italian cohort with progressive myopathy with specific pathology including rimmed ubiquitin-positive autophagic vacuolation. Suggested disease name myopathy with rimmed ubiquitin-positive autophagic vacuolation (MRUPAV). An additional 4 unrelated Chinese families/probands were reported. The repeat expansion is not detectable using short-read sequencing. Normal PLIN4 alleles: 27-31 x 33-mer Pathogenic: ≥39 x 33-mer Sources: Literature |
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| Mendeliome v1.1859 | SERPINA11 |
Ain Roesley gene: SERPINA11 was added gene: SERPINA11 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: SERPINA11 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SERPINA11 were set to 38831697 Review for gene: SERPINA11 was set to RED gene: SERPINA11 was marked as current diagnostic Added comment: 1 family with 2 fetuses. 1st fetus presented with isolated pericardial effusion and a TOP was opted. post mortem: mild subcutaneous edema with subtle facial dysmorphic features small gelatinous glistening cyst on the right pericardium. Bilateral pleural effusion and multiple similar cysts were noted on the lung surfaces 2nd fetus also presented with pleural and pericardial effusion and a TOP was opted post mortem findings were similar to fetus#1 homozygous nonsense variant in SERPINA11 was found p.(Tyr224*) Immunofluorescence of lung sections from fetus#1 and a gestation-matched fetus as a control demonstrated undetectable levels of SERPINA11 in the bronchiolar epithelium Sources: Literature |
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| Mendeliome v1.1749 | IL27RA |
Ain Roesley gene: IL27RA was added gene: IL27RA was added to Mendeliome. Sources: Literature Mode of inheritance for gene: IL27RA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL27RA were set to 38509369 Phenotypes for gene: IL27RA were set to Epstein-Barr virus infection MONDO:0005111 , IL27RA-related Review for gene: IL27RA was set to AMBER gene: IL27RA was marked as current diagnostic Added comment: 3 children from 2 families with severe acute EBV infection. fam1: homozygous for p.(Gln96*) (NMD-pred) fam2: chet for p.(Arg446Gly) and c.1142-2A>C the splice variant in fam2 was found to to result in an in-frame deletion p.(Gln381_Ala395del) the missense in fam2 is hypothesised to be a hypomorphic allele: - out of 15 Homs in the Finnish database, 2 had hospital diagnoses of EBV IM - expression of this variant on its own results in a weak but detectable IL-27RA expression associated with significant increase in STAT1/3 phosphorus in response to IL-27 stimulation borderline amber/green due to functional studies performed Sources: Literature |
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| Mendeliome v1.1071 | AQP4 |
Lucy Spencer gene: AQP4 was added gene: AQP4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AQP4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AQP4 were set to 37143309 Phenotypes for gene: AQP4 were set to ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448 Review for gene: AQP4 was set to AMBER Added comment: PMID: 37143309 Cohort of patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). Missense variant in AQP4 seen homozygous in 2 siblings and het in the parents. Patients had macrocephaly, developmental delay, hypotonia, epilepsy, and cognitive deficit. Western blots on generated MDCK cell lines showed no detectable expression of AQP4 protein from the cells with the patients variant. Immunofluorescence also showed no membrane expression. Overexpression studies in HEK293T cells showed WT was seen as mainly monomers or dimers where as variant protein formed large aggregates- likely due to the saturation of protein degradation pathways because of the overexpression. Sources: Literature |
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| Mendeliome v1.656 | EFCAB1 |
Chirag Patel gene: EFCAB1 was added gene: EFCAB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: EFCAB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EFCAB1 were set to PMID: 36727596 Phenotypes for gene: EFCAB1 were set to Primary ciliary dyskinesia and heterotaxy, no OMIM # Review for gene: EFCAB1 was set to GREEN Added comment: WES in 3 individuals with laterality defects and respiratory symptoms, identified homozygous pathogenic variants in CLXN (EFCAB1). They found Clxn expressed in mice left-right organizer. Transmission electron microscopy depicted outer dynein arm (ODA) defects in distal ciliary axonemes. Immunofluorescence microscopy revealed absence of CLXN from the ciliary axonemes, absence of the ODA components DNAH5, DNAI1 and DNAI2 from the distal axonemes, as well as mislocalization or absence of DNAH9. Additionally, CLXN is undetectable in ciliary axonemes of individuals with defects in the outer dynein arm docking (ODA-DC) machinery: ODAD1, ODAD2, ODAD3 and ODAD4. Moreover, SMED-EFCAB1-deficient planaria displayed ciliary dysmotility. Sources: Literature |
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| Mendeliome v1.44 | BUB1 |
Paul De Fazio gene: BUB1 was added gene: BUB1 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: BUB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BUB1 were set to 35044816; 19772675; 19117986; 23209306 Phenotypes for gene: BUB1 were set to Intellectual disability and microcephaly Review for gene: BUB1 was set to GREEN gene: BUB1 was marked as current diagnostic Added comment: 2 unrelated patients with ID, microcephaly, short stature, dysmorphic features reported with biallelic variants: P1 (3yo male): homozygous start-loss variant (2 hets and 0 hom in gnomAD). Functional testing showed a small amount of full-length protein was translated, and BUB1 recruitment to kinetochores was nearly undetectable. P2 (16yo female): compound heterozygous for a canonical splice variant (1 het and no hom in gnomAD) and an NMD-predicted frameshift variant (absent from gnomAD). The splice variant was shown to result in an in-frame deletion of 54 amino acids in the kinase domain. P2 cells have reduced protein levels but essentially no kinase activity. BUB1 patient cells have impaired mitotic fidelity. Homozygous Bub1 disruption in mice is embryonic lethal (PMID:19772675). A hypomorphic mouse is viable with increased tumourigenesis with ageing and aneuploidy (PMID:19117986). A kinase-dead mouse does not show increased tumourigenesis but does have a high frequency of aneuploid cells (PMID:23209306) Sources: Literature |
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| Mendeliome v0.11540 | NDUFAF4 |
Krithika Murali edited their review of gene: NDUFAF4: Added comment: 3 unrelated families reported with patient-specific functional evidence provided for each. PMID: 32949790 - report two siblings with facial dysmorphism and lactic acidosis diagnosed neonatally with subsequent fatal early encephalopathy with apneic episodes, irritability, central hypoventilation, liver involvement and hyperammonemia. Cerebral white matter anomalies reported in one patient and cardiomyopathy in the other. WES identified homozygous nonsense NDUFAF4 variants with absent NDUFAF4 expression in patient fibroblasts. OXPHOS assembly studies demonstrated almost undetectable levels of fully assembled complex I and complex I–containing supercomplexes and an abnormal accumulation of SCIII2IV1 supercomplexes. Morphologically, fibroblasts showed rounder mitochondria and a diminished degree of branching of the mitochondrial network. PMID: 28853723 - report one patient born at 38 weeks after IOL for IUGR. Presented age 7 months with developmental regression, growth failure and central hypotonia. Brain MRI revealed diffuse bilateral signal alterations in the basal ganglia and thalami and an EEG showed generalized slowing with multifocal spikes consistent with an epileptogenic focus. Homozygous missense NDUFAF4 variants identified. Lentiviral complementation of patient fibroblasts with wild-type NDUFAF4 rescued complex I deficiency and assembly defect PMID 18179882 - report multiple affected individuals from one family. Most presented soon after birth with severe metabolic acidosis and high plasma lactate levels. Patients who survived longer were repeatedly admitted because of exacerbation of the acidosis during intercurrent infections. One long-term survivor had profound ID.; Changed publications: 32949790, 28853723, 18179882 |
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| Mendeliome v0.10633 | DLX5 |
Zornitza Stark changed review comment from: A homozygous missense mutation (Q178P) was identified in 2 affected sisters from a consanguineous Yemeni family with split-hand/foot malformation and hearing loss, who had no detectable chromosomal aberration, Shamseldin et al. (2012). A heterozygosity missense mutation (Q186H) was identified in a 31-year-old Chinese woman with SHFM, Wang et al. (2014). A heterozygosity nonsense mutationIn (E39X) was identified in the probands from 2 unrelated Polish families with isolated SHFM, Sowinska-Seidler et al. (2014). Animal model evidence - mouse; to: A homozygous missense mutation (Q178P) was identified in 2 affected sisters from a consanguineous Yemeni family with split-hand/foot malformation and hearing loss, who had no detectable chromosomal aberration, Shamseldin et al. (2012). A heterozygosity missense mutation (Q186H) was identified in a 31-year-old Chinese woman with SHFM, Wang et al. (2014). A heterozygosity nonsense mutationIn (E39X) was identified in the probands from 2 unrelated Polish families with isolated SHFM, Sowinska-Seidler et al. (2014). Animal model evidence - mouse Green for mono-allelic, Amber for bi-allelic. |
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| Mendeliome v0.7615 | SEPT9 | Zornitza Stark edited their review of gene: SEPT9: Added comment: Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant form of recurrent focal neuropathy characterized clinically by acute, recurrent episodes of brachial plexus neuropathy with muscle weakness and atrophy preceded by severe pain in the affected arm. Multiple founder variants, including p.Arg88Trp. Also note intragenic duplication and 5'UTR variant reported, which may not be detectable by all NGS assays.; Changed publications: 16186812, 19451530, 19939853, 19139049 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4398 | SVBP |
Zornitza Stark changed review comment from: 5 unrelated families with homozygous mutations in SVBP. 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. 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 |
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| Mendeliome v0.2328 | TECTA | Zornitza Stark Marked gene: TECTA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2328 | TECTA | Zornitza Stark Added comment: Comment when marking as ready: Both recessive and dominant deafness associations assessed as DEFINITIVE by ClinGen. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2328 | TECTA | Zornitza Stark Gene: tecta has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2328 | TECTA | Zornitza Stark Phenotypes for gene: TECTA were changed from to Deafness, autosomal recessive 21 603629; Deafness, autosomal dominant 8/12 601543 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2327 | TECTA | Zornitza Stark Publications for gene: TECTA were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2326 | TECTA | Zornitza Stark Mode of pathogenicity for gene: TECTA was changed from to Other | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2325 | TECTA | Zornitza Stark Mode of inheritance for gene: TECTA was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2303 | TECTA | Elena Savva reviewed gene: TECTA: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID:22718023, 17136632, 31554319, 21520338; Phenotypes: Deafness, autosomal recessive 21 603629, Deafness, autosomal dominant 8/12 601543; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1777 | TIMMDC1 |
Zornitza Stark gene: TIMMDC1 was added gene: TIMMDC1 was added to Mendeliome. Sources: NHS GMS Mode of inheritance for gene: TIMMDC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TIMMDC1 were set to 28604674; 30981218 Phenotypes for gene: TIMMDC1 were set to Mitochondrial complex I deficiency, nuclear type 31 MIM#618251 Review for gene: TIMMDC1 was set to AMBER Added comment: A deep intronic variant (c.597-1340A>G, only detectable by WGS) that causes a splicing aberration was identified in a homozygous state in 3 unrelated cases from different ethnic backgrounds. A patient with Leigh-like syndrome had a homozygous stopgain variant in PDHX and a homozygous stopgain variant in TIMMDC1 (p.Arg225*). The TIMMDC1 mutant protein could still rescue complex I assembly in TIMMDC1 knockout cells and the patient’s clinical phenotype was not clearly distinct from that of other patients with the same PDHX defect. Sources: NHS GMS |
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| Mendeliome v0.322 | SVBP |
Zornitza Stark gene: SVBP was added gene: SVBP was added to Mendeliome_VCGS. Sources: Literature Mode of inheritance for gene: SVBP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SVBP were set to 31363758; 30607023 Phenotypes for gene: SVBP were set to Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly; OMIM #618569 Review for gene: SVBP was set to GREEN Added comment: 5 unrelated families with homozygous mutations in SVBP. 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 |
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| Mendeliome v0.0 | TECTA |
Zornitza Stark gene: TECTA was added gene: TECTA was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: TECTA was set to Unknown |
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