Zaspopathy in a large classic late-onset distal myopathy family

R. Griggs, A. Vihola, P. Hackman, K. Talvinen, H. Haravuori, G. Faulkner, B. Eymard, I. Richard, D. Selcen, A. Engel, O. Carpen, B. Udd

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


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 αB-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 αB-crystallin and α-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.

Original languageEnglish (US)
Pages (from-to)1477-1484
Number of pages8
Issue number6
StatePublished - Jun 2007


  • Distal myopathy
  • Myofibrillar myopathy
  • ZASP

ASJC Scopus subject areas

  • Clinical Neurology


Dive into the research topics of 'Zaspopathy in a large classic late-onset distal myopathy family'. Together they form a unique fingerprint.

Cite this