Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy

• DOI: 10.1073/pnas.96.5.2305
• Publication Date: 2002-07-26T14:42:40Z
• Authors: Katarina Pelin; Pirta Hilpelä; Kati Donner; Caroline Sewry; Patrick A. Akkari; Stephen D. Wilton; Duangrurdee Watta...; Marie-Louise Bang; Thomas Centner; Folker Hanefeld; Sylvie Odent; Michel Fardeau; J. Andoni Urtizberea; Francesco Muntoni; Victor Dubowitz; Alan H. Beggs; Nigel G. Laing; Siegfried Labeit; Albert de la Chap...; Carina Wallgren-P...
• Keywords: Nebulin; Nemaline myopathy; Compound heterozygosity; Congenital myopathy

The congenital nemaline myopathies are rare hereditary muscle disorders characterized by the presence in fibers of bodies consisting proteins derived from Z disc and thin filament. In a single large Australian family with an autosomal dominant form myopathy, disease is caused mutation α-tropomyosin gene TPM3 . typical myopathy inherited as recessive trait, locus which we previously assigned to chromosome 2q21.2-q22. We show here that mutations nebulin located within this region associated disease. protein giant found filaments striated muscle. A variety isoforms thought contribute molecular diversity discs. have studied 3′ end 20.8-kb cDNA encoding part 800-kDa describe six disease-associated patients five families different ethnic origins. two consanguineous parents, were homozygous for point mutations. one nonconsanguineous affected siblings compound heterozygotes mutations, further detected each, haplotypes compatible heterozygosity. Immunofluorescence studies antibodies specific C-terminal indicate may cause truncation possibly loss fiber-type diversity, be relevant pathogenesis.