Résumé :
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Background: Mutations in genes coding for thin filament components have been identified in structural congenital myopathies including nemaline myopathy, congenital fibre type disproportion, Cap disease and actin myopathy. Nemaline myopathies (NM) are characterized by the presence of rod structures in muscle and classified in seven sub-groups according to onset age and clinical features. Dominant, recessive and de novo mutations have been identified mostly in ACTA1 and Neb genes and, to a lower extend, in TPM2, TPM3, TNNT1 and CFL2 genes. Congenital fibre type disproportion (CFTD) is characterised by consistent hypotrophy of type 1 compared to type 2 fibres and associated with mutations in ACTA1, TPM3 and SEPN1 genes. We have studied a panel of 47 patients presenting with NM (37) or CFTD (8) and analysed ACTA1, TPM2, TPM3, TNNT1 and CFL2 genes by exon sequencing. When possible, NEB linkage studies have also been performed. Mutations have been identified in ACTA1 gene in 8 NM cases and one CFTD case , in TPM3 gene in 1 NM case and one CFTD case, in TPM2 gene in 2 NM cases and linkage to NEB gene in two further cases of NM. No mutation has been identified in TNNT1 and CFL2 genes in the remaining 24 NM cases (2/3). De novo ACTA1 missense mutations were mostly associated with severe or intermediate forms of NM or CFTD whereas missense mutations in TPM2, TPM3 but also ACTA1 genes were identified in dominant milder forms of NM. Furthermore, a recessive non-sense TPM2 mutation was identified in a new form of nemaline myopathy associated with a non-lethal multiple pterygium syndrome (Escobar variant). These results are in good agreement with the previously reported studies and confirm that mutations in additional genes or NEB gene must account for the majority of NM cases.
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