Muscular dystrophy and myopathy_Paediatric
Gene: TPM3
Variable age of onset due to the variability of phenotypes. Mutations in TPM3 cause a diverse group of congenital myopathies all characterised by muscle weakness/hypotonia.
AD Congenital Myopathy:
PMID: 26418456
Quantitative in vitro motility assay show that gain of function is mechanism of disease - mutations in the TPM3 gene led to an increased function in the myofibres/muscle cells.
2 unrelated individuals with ΔE218 and ΔE224 de novo deletions in TPM3 with muscle stiffness. Both muscle biopsies showed features of mild myopathy.
PMID: 18300303
4 individuals with phenotypic features of congenital myopathy and mutation present in TPM3
AR Congenital myopathy:
PMID: 10619715
Individual from consanguineous parents with severe symptoms of congenital myopathy
PMID: 12196661
Individual who is a compound heterozygote for nemaline myopathy
PMID: 18382475
Affected individuals from two turkish families with myopathy phenotypes.
Sources: OtherCreated: 9 May 2023, 4:21 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Congenital myopathy 4A, autosomal dominant (MIM#255310); Congenital myopathy 4B, autosomal recessive (MIM#609284)
Publications
Mode of pathogenicity
Other
Mutations in TPM3, encoding Tpm3.12, cause a clinically and histopathologically diverse group of myopathies characterised by muscle weakness.
Note report of two individuals with novel de novo Tpm3.12 single glutamic acid deletions at positions ΔE218 and ΔE224, resulting in a significant hypercontractile phenotype with congenital muscle stiffness, rather than weakness, and respiratory failure in one PMID 26418456. GOF proposed.Created: 16 Oct 2020, 8:53 a.m. | Last Modified: 16 Oct 2020, 8:53 a.m.
Panel Version: 0.291
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
CAP myopathy 1, MIM# 609284; Myopathy, congenital, with fiber-type disproportion, MIM# 255310; Nemaline myopathy 1, autosomal dominant or recessive, MIM# 609284; Congenital muscle stiffness
Publications
Mode of pathogenicity
Other
Gene: tpm3 has been classified as Green List (High Evidence).
Gene: tpm3 has been classified as Green List (High Evidence).
gene: TPM3 was added gene: TPM3 was added to Muscular dystrophy_Paediatric. Sources: Other Mode of inheritance for gene: TPM3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TPM3 were set to 26418456; 18300303; 10619715; 12196661; 18382475 Phenotypes for gene: TPM3 were set to Congenital myopathy 4A, autosomal dominant (MIM#255310); Congenital myopathy 4B, autosomal recessive (MIM#609284) Review for gene: TPM3 was set to GREEN