title: Homozygosity of the Dominant Myotilin c.179C>T (p.Ser60Phe) Mutation Causes a More Severe and Proximal Muscular Dystrophy.
abstract: Most myotilinopathy patients present with a dominant late onset distal phenotype and myofibrillar pathology, although the first MYOT mutation in a family reported to have LGMD phenotype. We report here a French family affected with a late onset proximal and distal muscle weakness and myofibrillar myopathy on muscle pathology, in which the siblings known to be clinically affected were homozygous for the c.179C>T (p.Ser60Phe) myotilin gene mutation. One subjectively asymptomatic member of the family was heterozygous for this mutation. This is the first report of a family with patients being homozygous for a known dominant MYOT mutation. Dominant negative mutations are generally considered not to cause a more severe disease in homozygosity, but our data clearly demonstrate the existence of dominant MYOT mutations with a possible dose effect causing a more severe disease phenotype in homozygosity in the spectrum of myofibrillar myopathies (MFM).
authors.affiliation: IGBMC, CNRS UMR 7104, INSERM U964, Strasbourg University, France.|Service de Neurologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Rudolf
authors.affiliation: Neuromuscular Research Unit, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Suominen
authors.affiliation: Neuromuscular Research Unit, University of Tampere and Tampere University Hospital, Tampere, Finland.
authors.forename: Sini
authors.initials: S
authors.lastname: Penttilä
authors.affiliation: Folkhälsan Institute of Genetics and Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Peter
authors.initials: P
authors.lastname: Hackman
authors.affiliation: Folkhälsan Institute of Genetics and Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Anni
authors.initials: A
authors.lastname: Evilä
authors.affiliation: Département d'Anatomopathologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Lannes
authors.affiliation: Service de Neurologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Andoni
authors.initials: A
authors.lastname: Echaniz-Laguna
authors.affiliation: Département de Radiologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bierry
authors.affiliation: IGBMC, CNRS UMR 7104, INSERM U964, Strasbourg University, France.|Service de Neurologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.|Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, Universitdé Strasbourg, INSERM, Illkirch, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Tranchant
authors.affiliation: Folkhälsan Institute of Genetics and Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland.|Département d'Anatomopathologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.|Department of Neurology, Vaasa Central Hospital, Vaasa, Finland.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Udd
mesh_terms: D000328:Adult; D000368:Aged; D064211:Connectin / Q000235:genetics*; D004576:Electromyography; D005260:Female; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D020914:Myopathies, Structural, Congenital / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010375:Pedigree; D012720:Severity of Illness Index; D035781:Siblings
chemical_list: D064211:Connectin; C577290:MYOT protein, human; D008840:Microfilament Proteins
keywords: MYOT; Molecular genetics; c.179C>T (p.Ser60Phe); myofibrillar myopathy; myotilin homozygosity