title: Novel Pathogenic Variants in a French Cohort Widen the Mutational Spectrum of GNE Myopathy.
abstract: BACKGROUND
  GNE myopathy is a rare autosomal recessively inherited muscle disease resulting from mutations in the gene encoding GNE (UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase), a key enzyme in sialic acid biosynthesis. 154 different pathogenic variants have been previously associated with GNE myopathy.
  
  
  OBJECTIVE
  Describe novel pathogenic variants associated with GNE myopathy in a large French cohort.
  
  
  METHODS
  We analyzed mutational data from 32 GNE myopathy index patients. Novel, as well as previously published pathogenic variants, were examined for possible deleterious effects on splicing.
  
  
  RESULTS
  We describe 13 novel pathogenic variants in GNE, identified in the first large French cohort reported to date. We also find that 6 published pathogenic variants might have a previously unrecognized deleterious effect on splicing.
  
  
  CONCLUSIONS
  Novel pathogenic GNE variants described here raise the total number of different pathogenic variants reported to 167, complementing the recently published GNE mutation update. Our novel findings on possible splice-disrupting effects by several variants suggest that the pathogenicity mechanism of these variants could be reinterpreted, expanding our knowledge about the GNE mutational spectrum.
authors.affiliation: Aix Marseille Université, INSERM, GMGF UMR_S 910, 13385, Marseille, France.|APHM, Département de Génétique Médicale, Hôpital Timone Enfants, 13385, Marseille, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Cerino
authors.affiliation: Aix Marseille Université, INSERM, GMGF UMR_S 910, 13385, Marseille, France.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Gorokhova
authors.affiliation: Institut de Myologie, APHP, Groupe Hospitalier La Pitié Salpêtrière, 75013, Paris, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Béhin
authors.affiliation: APHP, Hôpital Marin, 64700, Hendaye, France.
authors.forename: Jon Andoni
authors.initials: JA
authors.lastname: Urtizberea
authors.affiliation: Aix Marseille Université, INSERM, GMGF UMR_S 910, 13385, Marseille, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Kergourlay
authors.affiliation: APHM, Département de Génétique Médicale, Hôpital Timone Enfants, 13385, Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Salvo
authors.affiliation: APHM, Département de Génétique Médicale, Hôpital Timone Enfants, 13385, Marseille, France.
authors.forename: Rafaëlle
authors.initials: R
authors.lastname: Bernard
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lévy
authors.affiliation: Aix Marseille Université, INSERM, GMGF UMR_S 910, 13385, Marseille, France.|APHM, Département de Génétique Médicale, Hôpital Timone Enfants, 13385, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bartoli
authors.affiliation: Aix Marseille Université, INSERM, GMGF UMR_S 910, 13385, Marseille, France.|APHM, Département de Génétique Médicale, Hôpital Timone Enfants, 13385, Marseille, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Krahn
keywords: Distal myopathy with rimmed vacuoles; GNE; mutation; nonaka; splicing