title: Abnormal proliferation and spontaneous differentiation of myoblasts from a symptomatic female carrier of X-linked Emery-Dreifuss muscular dystrophy.
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.
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Meinke
authors.affiliation: Friedrich-Baur-Institut, Department of Neurology, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schneiderat
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Vlastimil
authors.initials: V
authors.lastname: Srsen
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Nadia
authors.initials: N
authors.lastname: Korfali
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Phú
authors.initials: P
authors.lastname: Lê Thành
authors.affiliation: Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, UK.
authors.forename: Graeme J M
authors.initials: GJ
authors.lastname: Cowan
authors.affiliation: Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Cavanagh
authors.affiliation: Institute of Human Genetics Greifswald, University Medicine, University of Greifswald, Germany (retired).
authors.forename: Manfred
authors.initials: M
authors.lastname: Wehnert
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK. Electronic address: e.schirmer@ed.ac.uk.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Schirmer
authors.affiliation: Friedrich-Baur-Institut, Department of Neurology, Ludwig-Maximilians-University of Munich, Munich, Germany. Electronic address: maggie.walter@lrz.uni-muenchen.de.
authors.forename: Maggie C
authors.initials: MC
authors.lastname: Walter
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015703:Antigens, CD; D001324:Autoantigens / Q000378:metabolism; D009202:Cardiomyopathies / Q000209:etiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002648:Child; D005192:Family Health; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D034904:Lamin Type A / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000150:complications / Q000235:genetics / Q000473:pathology*; D032446:Myoblasts / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D001324:Autoantigens; D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D034904:Lamin Type A; D008565:Membrane Proteins; D009687:Nuclear Proteins; C086074:PCM1 protein, human; D034741:RNA, Small Interfering; C092710:emerin
keywords: EMD; Emerin; Emery–Dreifuss muscular dystrophy; Myoblast differentiation; X-inactivation