title: A Study of a Cohort of X-Linked Myotubular Myopathy at the Clinical, Histologic, and Genetic Levels.
abstract: Myotubular myopathy is a rare X-linked congenital myopathy characterized by marked neonatal hypotonia and respiratory insufficiency, facial and ocular involvement, and muscle biopsy with prominent central nuclei in the majority of muscle fibers. It is caused by mutations in MTM1, which codes for the phosphoinositides phosphatase myotubularin. In this work, we established and detailed a new cohort of six patients at the clinical, histologic, and genetic levels.
  
  
  
  Patients were recruited after screening 3065 muscle biopsy reports from two large biopsy banks in Sao Paulo, Brazil from the years 2008 to 2013, and from referrals to a neuromuscular outpatient clinic between 2011 and 2013. We reviewed biopsy slides, evaluated patients, and Sanger sequenced MTM1 in the families.
  
  
  
  All patients but one had classic phenotypes with a stable course after a severe onset. Two patients died suddenly from hypovolemic shock. Muscle biopsies had been performed in five patients, all of whom showed a classic pattern with a predominance of centrally located nuclei and increased oxidative activity in the center of the fibers. Two patients showed necklace fibers, and two families had novel truncating mutations in MTM1.
  
  
  
  X-linked myotubular myopathy is rare in the Brazilian population. Necklace fibers might be more prevalent in this condition than previously reported. Direct Sanger sequencing of MTM1 on clinical suspicion avoids the need of a muscle biopsy.
authors.affiliation: Departamento de Neurologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.
authors.forename: Osorio
authors.initials: O
authors.lastname: Abath Neto
authors.affiliation: Departamento de Biofísica, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Marina Rodrigues E
authors.initials: MR
authors.lastname: Silva
authors.affiliation: Departamento de Neurologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.
authors.forename: Cristiane de Araújo
authors.initials: Cde A
authors.lastname: Martins
authors.affiliation: Setor de Doenças Neuromusculares, Departamento de Neurologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Acary de Souza Bulle
authors.initials: Ade S
authors.lastname: Oliveira
authors.affiliation: Departamento de Neurologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.
authors.forename: Umbertina Conti
authors.initials: UC
authors.lastname: Reed
authors.affiliation: Faculté de Médecine, Laboratoire de Diagnostic Génétique, Nouvel Hopital Civil, Strasbourg, France; Department of Translational Medicine and Neurogenetics, IGBMC, INSERM U964, CNRS UMR7104, University of Strasbourg, Collège de France, Illkirch, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Biancalana
authors.affiliation: Departamento de Biofísica, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: João Bosco
authors.initials: JB
authors.lastname: Pesquero
authors.affiliation: Department of Translational Medicine and Neurogenetics, IGBMC, INSERM U964, CNRS UMR7104, University of Strasbourg, Collège de France, Illkirch, France.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Laporte
authors.affiliation: Departamento de Neurologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil. Electronic address: edmar.zanoteli@usp.br.
authors.forename: Edmar
authors.initials: E
authors.lastname: Zanoteli
mesh_terms: D001706:Biopsy; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005145:Face / Q000002:abnormalities; D006801:Humans; D007223:Infant; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology*; D020914:Myopathies, Structural, Congenital / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D010641:Phenotype; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics*
chemical_list: D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin
keywords: MTM1; centronuclear myopathy; congenital myopathy; myotubular myopathy; myotubularin