A second pedigree with autosomal dominant nemaline myopathy caused by TPM3 mutation: a clinical and pathological study.
The slow alpha-tropomyosin (TPM3) gene has to date been associated with few cases of both dominant and recessive nemaline myopathies. We report the identification of a p.Arg167His mutation in a four-generation family presenting with a mild classical form of the disease. Clinically, there was no correlation between the age at presentation and the severity of the disease. The dominant-negative p.Arg167His mutation is a recurrent mutation, previously reported in one sporadic case. Histological studies showed discrepancy between the two reports. While a type II fibre predominance was described in the sporadic case, we observed an almost complete type I fibre predominance. This study emphasizes the variability in histopathological phenotypes seen with TPM3 mutations.
Pénisson-Besnier
Isabelle
I
Centre de Référence Maladies Neuromusculaires de l'Enfant et de l'Adulte, Nantes-Angers, France. ispenisson-besnier@chu-angers.fr
Monnier
Nicole
N
Toutain
Annick
A
Dubas
Frédéric
F
Laing
Nigel
N
D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000235:genetics; D005192:Family Health; D005260:Female; D006639:Histidine / Q000235:genetics; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009154:Mutation; D017696:Myopathies, Nemaline / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D014335:Tropomyosin / Q000235:genetics*
C498783:TPM3 protein, human; D014335:Tropomyosin; D006639:Histidine; D001120:Arginine