Activity

Filter

Cancel
Date Panel Item Activity
13 actions
Congenital myopathy v7.77 TUBA4A Achchuthan Shanmugasundram changed review comment from: 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.

Of the three families with homozygous variants, the disease onset/ first clinical examination was only after 10 years in two (although motor delay reported in one family) and the third was 70-year-old patient also with a VUS variant in FLNC gene.

This gene has been associated only with AD congenital myopathy in OMIM (MIM #621225) and the record was last accessed 09 June 2026.; to: 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.

Of the three families with homozygous variants, the disease onset/ first clinical examination was only after 10 years in two (although motor delay reported in one family) and the third was 60-year-old patient with a VUS variant in FLNC gene, which has since been reported as LB in ClinVar.

This gene has been associated only with AD congenital myopathy in OMIM (MIM #621225) and the record was last accessed 09 June 2026.
Congenital myopathy v3.41 FLNC Arina Puzriakova Phenotypes for gene: FLNC were changed from Myopathy, distal, 4, OMIM:614065; Distal myopathy with posterior leg and anterior hand involvement, MONDO:0013550; Myopathy, myofibrillar, 5, OMIM:609524; Myopathy, myofibrillar, 5, MONDO:0012289 to Myopathy, distal, 4, OMIM:614065; Myopathy, myofibrillar, 5, OMIM:609524
Congenital myopathy v2.12 FLNC Arina Puzriakova Phenotypes for gene: FLNC were changed from Myopathy, myofibrillar, 5, 609524; early-onset restrictive cardiomyopathy and congenital myopathy to Myopathy, distal, 4, OMIM:614065; Distal myopathy with posterior leg and anterior hand involvement, MONDO:0013550; Myopathy, myofibrillar, 5, OMIM:609524; Myopathy, myofibrillar, 5, MONDO:0012289
Congenital myopathy v1.213 FLNC Louise Daugherty Source Expert Review was added to FLNC.
Source NHS GMS was added to FLNC.
Congenital myopathy v1.208 FLNC Louise Daugherty Classified gene: FLNC as Amber List (moderate evidence)
Congenital myopathy v1.208 FLNC Louise Daugherty Added comment: Comment on list classification: Amber gene recommended by Anna Sarkozy as a result of GLH Test Group prior to sign off. Four unrelated patients with cardiomyopathy, arthrogryposis, and a limb-girdle pattern of skeletal muscle weakness at birth or during the first year of life harboured de novo missense variants; three of these patients had p.Ala1186Val.
Kiselev A, Vaz R, Knyazeva A, et al. : De novo mutations in FLNC leading to early-onset restrictive cardiomyopathy and congenital myopathy. Hum Mutat. 2018;39(9):1161–72. 10.1002/humu.23559
Congenital myopathy v1.208 FLNC Louise Daugherty Gene: flnc has been classified as Amber List (Moderate Evidence).
Congenital myopathy v1.207 FLNC Louise Daugherty Publications for gene: FLNC were set to
Congenital myopathy v1.206 FLNC Louise Daugherty Phenotypes for gene: FLNC were changed from Myopathy, myofibrillar, 5, 609524 to Myopathy, myofibrillar, 5, 609524; early-onset restrictive cardiomyopathy and congenital myopathy
Congenital myopathy v1.205 FLNC Louise Daugherty Mode of inheritance for gene: FLNC was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital myopathy FLNC Anna Sarkozy reviewed FLNC
Congenital myopathy FLNC Helen Brittain marked FLNC as ready
Congenital myopathy FLNC Helen Brittain reviewed FLNC