Abnormal proliferation and spontaneous differentiation of myoblasts from a symptomatic female carrier of X-linked Emery-Dreifuss muscular dystrophy

Peter Meinke, Peter Schneiderat, Vlastimil Srsen, Nadia Korfali, Phú Lê Thành, Graeme J M Cowan, David R. Cavanagh, Manfred Wehnert, Eric C. Schirmer*, Maggie C. Walter

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Emery-Dreifuss muscular dystrophy (EDMD) is a neuromuscular disease characterized by early contractures, slowly progressive muscular weakness and life-threatening cardiac arrhythmia that can develop into cardiomyopathy. In X-linked EDMD (EDMD1), female carriers are usually unaffected. Here we present a clinical description and in vitro characterization of a mildly affected EDMD1 female carrying the heterozygous EMD mutation c.174_175delTT; p.Y59* that yields loss of protein. Muscle tissue sections and cultured patient myoblasts exhibited a mixed population of emerin-positive and -negative cells; thus uneven X-inactivation was excluded as causative. Patient blood cells were predominantly emerin-positive, but considerable nuclear lobulation was observed in non-granulocyte cells - a novel phenotype in EDMD. Both emerin-positive and emerin-negative myoblasts exhibited spontaneous differentiation in tissue culture, though emerin-negative myoblasts were more proliferative than emerin-positive cells. The preferential proliferation of emerin-negative myoblasts together with the high rate of spontaneous differentiation in both populations suggests that loss of functional satellite cells might be one underlying mechanism for disease pathology. This could also account for the slowly developing muscle phenotype.

Original languageEnglish
Pages (from-to)127-136
Number of pages10
JournalNeuromuscular Disorders
Volume25
Issue number2
DOIs
Publication statusPublished - Feb 2015

Keywords

  • EMD
  • Emerin
  • Emery-Dreifuss muscular dystrophy
  • Myoblast differentiation
  • X-inactivation

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