title: Phenotype of matrin-3-related distal myopathy in 16 German patients.
abstract: OBJECTIVE
  To characterize the phenotype of patients with distal myopathy with vocal cord and pharyngeal weakness due to the p.S85C mutation in the matrin-3 gene (MATR3, Mendelian Inheritance in Man 164015). Recently, it has been suggested that patients with this mutation may suffer from familial amyotrophic lateral sclerosis.
  
  
  METHODS
  Sixteen patients from 6 families with late onset distal myopathy associated with the p.S85C MATR3 mutation were characterized.
  
  
  RESULTS
  Patients had a predominantly distal muscle weakness, most severely affecting ankle and wrist dorsiflexion. Relevant proximal and axial weakness was found in 6 and respiratory impairment in 5 patients. Dysphagia was diagnosed in 6 and mild voice abnormalities were found in 7 patients. However, laryngoscopy revealed normal vocal cord function. Creatine kinase was normal or mildly elevated. Electromyographically, spontaneous activity was found in 10 of 14 patients and complex repetitive discharges in 9 of 14 patients. Magnetic resonance imaging revealed severe fatty degeneration of distal and upper posterior leg and of paraspinal muscles. Histopathology ranged from mild myopathic to severe dystrophic changes including vacuoles. Absence of sarcomeres in the perinuclear region and abnormal invaginations of nuclei were found ultrastructurally. Haplotype analysis showed a common disease-specific haplotype of the 6 families and suggested that these families form a separate cluster.
  
  
  CONCLUSIONS
  In contrast to the 2 previously reported families, MATR3-related distal myopathy might be associated with relevant axial, proximal, and respiratory muscle weakness but without vocal cord palsy. There were no clinical, electrophysiological, or histopathological signs of lower motor neuron involvement.
authors.affiliation: Department of Neurology, Martin Luther University of Halle-Wittenberg, Halle, Germany.
authors.forename: Tobias J
authors.initials: TJ
authors.lastname: Müller
authors.forename: Torsten
authors.initials: T
authors.lastname: Kraya
authors.forename: Gisela
authors.initials: G
authors.lastname: Stoltenburg-Didinger
authors.forename: Frank
authors.initials: F
authors.lastname: Hanisch
authors.forename: Malte
authors.initials: M
authors.lastname: Kornhuber
authors.forename: Dietrich
authors.initials: D
authors.lastname: Stoevesandt
authors.forename: Jan
authors.initials: J
authors.lastname: Senderek
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.forename: Petra
authors.initials: P
authors.lastname: Baum
authors.forename: Marcus
authors.initials: M
authors.lastname: Deschauer
authors.forename: Stephan
authors.initials: S
authors.lastname: Zierz
mesh_terms: D000328:Adult; D017668:Age of Onset; D003680:Deglutition Disorders / Q000235:genetics / Q000473:pathology; D049310:Distal Myopathies / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005858:Germany; D006239:Haplotypes; D006334:Heart Function Tests; D006801:Humans; D007818:Laryngeal Diseases / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000235:genetics / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics*; D010608:Pharyngeal Diseases / Q000235:genetics* / Q000473:pathology*; D016601:RNA-Binding Proteins / Q000235:genetics*; D012129:Respiratory Function Tests; D012132:Respiratory Muscles / Q000473:pathology; D014832:Voice Disorders / Q000235:genetics / Q000473:pathology; D055815:Young Adult
chemical_list: C518587:MATR3 protein, human; D034521:Nuclear Matrix-Associated Proteins; D016601:RNA-Binding Proteins