Aktuelle Neurologie 2009; 36 - V376
DOI: 10.1055/s-0029-1238491

Autosomal dominant distal vacuolar myopathy associated with mutation of the nuclear matrix protein matrin 3

J Senderek 1, SM Garvey 1, M Krieger 1, I Tournev 1, M Elbracht 1, A Roos 1, C Stendel 1, A Uritzberea 1, V Guergueltcheva 1, V Mihailova 1, H Feit 1, J Tramonte 1, P Hedera 1, C Bergmann 1, S Rudnik-Schöneborn 1, K Zerres 1, H Lochmüller 1, E Seboun 1, JS Beckmann 1, MA Hauser 1, CE Jackson 1, J Weis 1
  • 1Zürich, CH; Charlottesville, USA; Aachen; Sofia, BG; Hendaye, F; Detroit, Temple, Nashville, USA; Newcastle upon Tyne, UK; Paris, F; Lausanne, CH; Durham, USA

Inherited distal myopathies represent a heterogeneous group of skeletal muscle disorders. One type of adult-onset, progressive autosomal dominant distal myopathy, frequently associated with dysphagia and dysphonia, has been mapped to chromosome 5q31 in a North American pedigree (vocal cord and pharyngeal weakness with distal myopathy; VCPDM). We recently identified a second large VCPDM family of Bulgarian descent and performed fine mapping of the critical interval. Sequencing of positional candidate genes revealed precisely the same non-conservative S85C missense mutation affecting an interspecies conserved residue in the MATR3 gene in both families (Senderek et al., Am J Human Genet, in press). MATR3 is expressed in skeletal muscle and encodes matrin 3, a component of the proteinaceous network that extends throughout the nucleus and has been termed the nuclear matrix. Different disease related haplotype signatures in the two families provide evidence that two independent mutational events at the same position in MATR3 cause VCPDM. Histopathological and electron microscopical analysis of two muscle biopsies revealed reduced matrin 3 immunoreactivity of muscle fiber nuclei and myonuclear degeneration as well as autophagic vacuoles in affected muscle fibers.