title: Genetic Characterization of a French Cohort of GNE-mutation negative inclusion body myopathy patients with exome sequencing.
abstract: BACKGROUND
  Hereditary inclusion body myopathy (hIBM) refers to a group of clinically and genetically heterogeneous diseases. The overlapping histochemical features of hIBM with other genetic disorders lead to low diagnostic rates with targeted single-gene sequencing. This is true for the most prevalent form of hIBM, GNEpathy. Therefore, we used whole-exome sequencing (WES) to determine whether a cohort of clinically suspected GNEpathy patients undiagnosed by targeted GNE analysis could be genetically characterized.
  
  
  METHODS
  Twenty patients with hIBM but undiagnosed by targeted GNE sequencing were analyzed by WES before data filtering on 306 genes associated with neuromuscular disorders.
  
  
  RESULTS
  Seven patients out of 20 were found to have disease-causing mutations in genes associated with hIBM or genes allowing for hIBM in the differential diagnosis or associated with unexpected diagnosis.
  
  
  CONCLUSIONS
  Next-generation sequencing is an efficient strategy in the context of hIBM, resulting in a molecular diagnosis for 35% of the patients initially undiagnosed by targeted GNE analysis. Muscle Nerve 56: 993-997, 2017.
authors.affiliation: Aix Marseille University, GMGF, INSERM AMU UMR_S910, Faculté de Médecine de Marseille, 4e étage Aile Verte, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.|APHM, Hôpital Timone Enfants, Département de Génétique Médicale, Marseille, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Cerino
authors.affiliation: Aix Marseille University, GMGF, INSERM AMU UMR_S910, Faculté de Médecine de Marseille, 4e étage Aile Verte, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Gorokhova
authors.affiliation: APHP, G.H. Pitié Salpêtrière, Centre de Référence Maladies Neuromusculaires Paris-Est, Institut de Myologie, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Laforet
authors.affiliation: APHP, G.H. Pitié Salpêtrière, Centre de Référence Maladies Neuromusculaires Paris-Est, Institut de Myologie, Paris, France.|Sorbonne Universités, UPMC University of Paris 06, Inserm UMRS974, CNRS FRE3617, Center for Research in Myology, Institut de Myologie, G.H. Pitié Salpêtrière, Paris, France.
authors.forename: Rabah
authors.initials: R
authors.lastname: Ben Yaou
authors.affiliation: Aix Marseille University, GMGF, INSERM AMU UMR_S910, Faculté de Médecine de Marseille, 4e étage Aile Verte, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.|APHM, Hôpital La Timone, Centre de Référence des Maladies Neuromusculaires et de la SLA, Marseille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Salort-Campana
authors.affiliation: Aix Marseille University, GMGF, INSERM AMU UMR_S910, Faculté de Médecine de Marseille, 4e étage Aile Verte, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.|APHM, Hôpital La Timone, Centre de Référence des Maladies Neuromusculaires et de la SLA, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Pouget
authors.affiliation: Aix Marseille University, GMGF, INSERM AMU UMR_S910, Faculté de Médecine de Marseille, 4e étage Aile Verte, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.|APHM, Hôpital La Timone, Centre de Référence des Maladies Neuromusculaires et de la SLA, Marseille, France.
authors.forename: Shahram
authors.initials: S
authors.lastname: Attarian
authors.affiliation: APHP, G.H. Pitié Salpêtrière, Centre de Référence Maladies Neuromusculaires Paris-Est, Institut de Myologie, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Eymard
authors.affiliation: Centre National de Génotypage, Institut de Génomique, CEA, Evry, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Deleuze
authors.affiliation: Centre National de Génotypage, Institut de Génomique, CEA, Evry, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Boland
authors.affiliation: APHP, G.H. Pitié Salpêtrière, Centre de Référence Maladies Neuromusculaires Paris-Est, Institut de Myologie, Paris, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Behin
authors.affiliation: APHP, G.H. Pitié Salpêtrière, Centre de Référence Maladies Neuromusculaires Paris-Est, Institut de Myologie, Paris, France.
authors.forename: Tanya
authors.initials: T
authors.lastname: Stojkovic
authors.affiliation: Sorbonne Universités, UPMC University of Paris 06, Inserm UMRS974, CNRS FRE3617, Center for Research in Myology, Institut de Myologie, G.H. Pitié Salpêtrière, Paris, France.
authors.forename: Gisele
authors.initials: G
authors.lastname: Bonne
authors.affiliation: Aix Marseille University, GMGF, INSERM AMU UMR_S910, Faculté de Médecine de Marseille, 4e étage Aile Verte, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.|APHM, Hôpital Timone Enfants, Département de Génétique Médicale, Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Levy
authors.affiliation: Aix Marseille University, GMGF, INSERM AMU UMR_S910, Faculté de Médecine de Marseille, 4e étage Aile Verte, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.|APHM, Hôpital Timone Enfants, Département de Génétique Médicale, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bartoli
authors.affiliation: Aix Marseille University, GMGF, INSERM AMU UMR_S910, Faculté de Médecine de Marseille, 4e étage Aile Verte, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.|APHM, Hôpital Timone Enfants, Département de Génétique Médicale, Marseille, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Krahn
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D018979:Myositis, Inclusion Body / Q000235:genetics*; D010641:Phenotype
chemical_list: D009097:Multienzyme Complexes; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase
keywords: GNE; NGS; diagnosis; exome; hIBM; myopathy