Elsevier

Neuromuscular Disorders

Volume 25, Issue 2, February 2015, Pages 127-136
Neuromuscular Disorders

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

https://doi.org/10.1016/j.nmd.2014.09.012Get rights and content
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Highlights

  • X-linked female presenting with EDMD1 not explained by uneven X-inactivation.

  • First EDMD blood phenotype with highly lobulated lymphocytes in EDMD1 patient.

  • Found high incidence of spontaneous differentiation in cultured patient myoblasts.

  • Faster proliferation of emerin-null than emerin-positive EDMD1 patient myoblasts.

  • Loss of satellite cells from the above might explain EDMD pathology.

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.

Keywords

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

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1

These authors contributed equally to the work.