Zaspopathy in a large classic late-onset distal myopathy family

R. Griggs, Anna Vihola, Peter Hackman, Kati Talvinen, Henna Haravuori, Georgine Faulkner, Bruno Eymard, Isabelle Richard, D Selcen, Andrew Engel, Olli Carpen, Bjarne Udd

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    Sammanfattning

    Distal myopathies have been associated with mutations in titin, dysferlin, GNE, desmin and myosin. Of these, only titin mutations were previously known to cause dominant late-onset distal myopathy. Recent findings, however, have indicated that patients affected with myofibrillar myopathy have a more distal than proximal muscle phenotype and a proportion of these may have mutations in myotilin, ZASP or filamin C, besides previously known desmin and alpha B-crystallin. Here we report that the disorder in one of the well-characterized autosomal dominant distal myopathy families, the Markesbery et al. family, first reported in 1974, is caused by ZASP mutation A165V. Previous linkage to the titin locus 2q31 proved incorrect. ZASP expression by immunoblotting shows normal presence of the main 32 and 78 kDa bands and immunohistochemistry in patients reveals normal Z-disc localization except for moderate accumulations together with myotilin, desmin alpha B-crystallin and alpha-actinin. Muscle imaging reveals involvement in both the posterior and anterior compartments of the lower leg and considerable affection of proximal leg muscles at later stages. Haplotype studies in this family and in five other unrelated families with European ancestry carrying the identical A165V mutation share common markers at the locus suggesting the existence of a founder mutation.
    Originalspråkengelska
    TidskriftBrain : a journal of neurology
    Volym130
    UtgåvaPt 6
    Sidor (från-till)1477-1484
    Antal sidor8
    ISSN0006-8950
    DOI
    StatusPublicerad - 2007
    MoE-publikationstypA1 Tidskriftsartikel-refererad

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