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| Motor Neurone Disease v1.24 | TUBA4A | Bryony Thompson Publications for gene: TUBA4A were set to 25374358; 25893256; 28069311; 38463699; 38884572; 26675813 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v1.23 | TUBA4A | Bryony Thompson Publications for gene: TUBA4A were set to 28069311; 25374358; 26675813 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v1.22 | TUBA4A | Bryony Thompson Classified gene: TUBA4A as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v1.22 | TUBA4A | Bryony Thompson Gene: tuba4a has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v1.21 | TUBA4A |
Bryony Thompson edited their review of gene: TUBA4A: Added comment: At least 13 probands reported with ALS or phenotype including motor neurone involvement. Limited segregation evidence and mechanism of disease not established - toxic gain of function, dominant negative, or loss of function suggested PMID: 25374358 - 7 rare TUBA4A variants OR = 36 [95% CI: 10–210], p = 4.3 × 10−7, Pcorrected = 4.2 × 10−3 in an FALS cohort. Included 1 nonsense (W407X in last exon) and 6 missense variants. FALS cases n=635, controls n=5,510. T145P variant segregated with disease within the family, while K430N was not detected in an affected first cousin of the sequenced proband (?phenocopy). Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability - suggesting a dominant negative mechanism of disease. PMID: 25893256 - 4 Italian sporadic ALS cases with rare TUBA4A variants (3 missense & 1 splice variant). Minigene assay demonstrates c.226+4A>G causes exon 2 skipping which is expected to a frameshift and NMD. Loss of function is not an established mechanism of ALS in relation to TUBA4A. PMID: 28069311 - rare missense (Thr381Met) detected in 2 siblings with ALS, but both had the C9orf72 expansion PMID: 38463699 - reduced TUBA4A protein expression in familial and sporadic ALS brain tissue. Knockout zebrafish has a motor axonopathy and motor behavior defects reflecting a motor neuron disease phenotype PMID: 38884572 - Multicentre cohort of 12 patients from 11 unrelated families presenting with ataxia age of onset 2-60 yrs (9 different missense variants). Amyotrophy or upper limb muscular weakness in 2/12, 16.6%.; Changed rating: GREEN; Changed publications: 25374358, 25893256, 28069311, 38463699, 38884572; Changed phenotypes: amyotrophic lateral sclerosis type 22 MONDO:0014531; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
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| Motor Neurone Disease v0.58 | TUBA4A | Zornitza Stark Marked gene: TUBA4A as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v0.58 | TUBA4A | Zornitza Stark Gene: tuba4a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v0.58 | TUBA4A | Zornitza Stark Phenotypes for gene: TUBA4A were changed from to Amyotrophic lateral sclerosis 22 with or without frontotemporal dementia, MIM# 616208 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v0.57 | TUBA4A | Zornitza Stark Publications for gene: TUBA4A were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v0.56 | TUBA4A | Zornitza Stark Mode of inheritance for gene: TUBA4A was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v0.55 | TUBA4A | Zornitza Stark Classified gene: TUBA4A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v0.55 | TUBA4A | Zornitza Stark Gene: tuba4a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v0.54 | TUBA4A | Zornitza Stark reviewed gene: TUBA4A: Rating: AMBER; Mode of pathogenicity: None; Publications: 28069311, 25374358, 26675813; Phenotypes: Amyotrophic lateral sclerosis 22 with or without frontotemporal dementia, MIM# 616208; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v0.0 | TUBA4A |
Zornitza Stark gene: TUBA4A was added gene: TUBA4A was added to Motor neuron disease MND_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Complex Neurology Flagship Mode of inheritance for gene: TUBA4A was set to Unknown |
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