title: A locus on chromosome 15q for a dominantly inherited nemaline myopathy with core-like lesions.
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), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1). In addition, mutations in the ryanodine receptor gene (RYR1) 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 (TPM1) located within this region is the strongest candidate gene. However, no mutations were found in the protein-coding region of TPM1, 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.
authors.affiliation: Neuromuscular Centre, Nijmegen Institute of Neurology, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. b.vanengelen@neuro.umcn.nl
authors.forename: I M P
authors.initials: IM
authors.lastname: Gommans
authors.forename: M
authors.initials: M
authors.lastname: Davis
authors.forename: K
authors.initials: K
authors.lastname: Saar
authors.forename: M
authors.initials: M
authors.lastname: Lammens
authors.forename: F
authors.initials: F
authors.lastname: Mastaglia
authors.forename: P
authors.initials: P
authors.lastname: Lamont
authors.forename: G
authors.initials: G
authors.lastname: van Duijnhoven
authors.forename: H J
authors.initials: HJ
authors.lastname: ter Laak
authors.forename: A
authors.initials: A
authors.lastname: Reis
authors.forename: O J M
authors.initials: OJ
authors.lastname: Vogels
authors.forename: N
authors.initials: N
authors.lastname: Laing
authors.forename: B G M
authors.initials: BG
authors.lastname: van Engelen
authors.forename: H
authors.initials: H
authors.lastname: Kremer
mesh_terms: D000293:Adolescent; D000328:Adult; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D018482:Muscle, Skeletal / Q000473:pathology; D017696:Myopathies, Nemaline / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D014335:Tropomyosin / Q000235:genetics
chemical_list: D014335:Tropomyosin