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A locus on chromosome 15q for a dominantly inherited nemaline myopathy with core-like lesions

Item Type:Article
Title:A locus on chromosome 15q for a dominantly inherited nemaline myopathy with core-like lesions
Creators Name:Gommans, I.M.P. and Davis, M. and Saar, K. and Lammens, M. and Mastaglia, F. and Lamont, P. and Van Duijnhoven, G. and Ter Laak, H.J. and Reis, A. and Vogels, O.J.M. and Laing, N. and van Engelen, B.G.M. and Kremer, H.
Abstract:Nemaline myopathy is a congenital neuromuscular disorder characterized by muscle weakness and the presence of nemaline rods. Five genes have now been associated with nemaline myopathy: {alpha}-tropomyosin-3 (TPM3), α-actin (ACTAI), nebulin (NEB), {beta}-tropomysin (TPM2) and troponin T (TNNT1). In addition, mutations in the ryanodine receptor gene (RYRI) have been associated with core-rod myopathy. Here we report linkage in two unrelated families, with a variant of nemaline myopathy, with associated core-like lesions. The clinical phenotype consists of muscle weakness in addition to a peculiar kind of muscle slowness. A genome-wide scan revealed a locus for nemaline myopathy with core-like lesions on chromosome 15q21-q23 for both families. Combining the two families gave a two-point LOD score of 10.65 for D15S993. The {alpha}-tropomyosin-1 gene (TPMI) located within this region is the strongest candidate gene. However, no mutations were found in the protein-coding region of TPMI, although small deletions or mutations in an intron cannot be excluded. The critical region contains few other candidate genes coding for muscle proteins and several genes of unknown function, and has not yet been sequenced completely. The novel phenotype of nemaline myopathy in the two presented families corresponds to an also novel, as yet uncharacterized, genotype.
Keywords:Nemaline, Myopathy, Genotype, Core, Chromosome 15
Publisher:Oxford University Press
Page Range:1545-1551
Date:July 2003
Official Publication:https://doi.org/10.1093/brain/awg162
PubMed:View item in PubMed

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