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| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v6.13 | TUBA4A | Achchuthan Shanmugasundram Tag Q2_26_promote_green tag was added to gene: TUBA4A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v6.13 | TUBA4A | Achchuthan Shanmugasundram Classified gene: TUBA4A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v6.13 | TUBA4A | Achchuthan Shanmugasundram Added comment: Comment on list classification: There are several unrelated families reported with monoallelic TUBA4A variants and three unrelated families with biallelic TUBA4A variants. Hence, this gene can be considered for promotion to green rating with 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' MOI in the next GMS update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v6.13 | TUBA4A | Achchuthan Shanmugasundram Gene: tuba4a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v6.12 | TUBA4A |
Achchuthan Shanmugasundram gene: TUBA4A was added gene: TUBA4A was added to Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies. Sources: Literature Mode of inheritance for gene: TUBA4A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TUBA4A were set to 38413182; 41678358 Phenotypes for gene: TUBA4A were set to Congenital myopathy 26, OMIM:621225; congenital myopathy 26, MONDO:0979229 Review for gene: TUBA4A was set to GREEN Added comment: PMID:38413182 (2024) reported the identification of a recurrent novel heterozygous de novo variant (c.679C>T/ p.Leu227Phe) in the TUBA4A gene in two unrelated Chinese patients with sporadic congenital myopathy (14-year-old and 6-year-old females). The prominent myopathological changes in both patients were muscle fibres with focal myofibrillar disorganisation and rimmed vacuoles. Immunofluorescence showed ubiquitin-positive TUBA4A protein aggregates in the muscle fibres with rimmed vacuoles. Overexpression of the L227F variant TUBA4A resulted in cytoplasmic aggregates which colocalised with ubiquitin in cellular model. PMID:41678358 (2026) reported a multi-centre study in which the authors identified one previously reported and 12 novel TUBA4A missense variants in 31 individuals from 19 unrelated families. Individuals in 17 families presented with a myopathy without any CNS involvement or history of such disease, while probands from the remaining two families presented with cerebellar ataxia and epilepsy accompanying proximal and axial muscle weakness along with protein aggregation. Four families demonstrated autosomal dominant transmission through heterozygous variants in TUBA4A, three probands had recessive inheritance due to homozygous variants, while the respective heterozygous carriers were asymptomatic; five probands carried de novo variants, and nine probands with heterozygous variants were classified as sporadic cases. Clinical phenotypes ranged from mild to severe myopathy, predominantly affecting the axial and paraspinal muscles. The disease onset ranged from congenital to late adulthood. Three families with heterozygous variants and one with homozygous variant presented with myofibrillar disorganisation. The following are details of the three patients with biallelic variants: - Patient 26 (homozygous for c. 34G>A/ p.Ala12Thr) - myofibrillar myopathy with prominent axial muscle weakness, late-onset ataxia with cerebellar atrophy, nemaline bodies, proteinopathy. Age of onset at 60 years. The patient was also identified with a VUS variant in FLCN gene, which has since been reported as LB in ClinVar. - Patient 21 (homozygous for c.722C>T/ p.Ser241Phe) - phenotype of myopathy / myo-tubulinopathy with fatigability and severe distal and proximal upper and lower limb weakness. Age of onset at 12 years. - Patients 22/23 (siblings homozygous for c.1061G>A/ p.Gly354Asp) - phenotype listed as myopathy / myo-tubulinopathy with fatigability and generalised symmetrical weakness (distal and proximal). Age of onset from first year. This gene has been associated only with AD congenital myopathy in OMIM (MIM #621225) and the record was last accessed 25 June 2026. Sources: Literature |
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