title: Vocal cord and diaphragm paralysis, as clinical features of a French family with autosomal recessive Charcot-Marie-Tooth disease, associated with a new mutation in the GDAP1 gene.
abstract: Axonal forms of Charot-Marie-Tooth disease, either dominantly or recessively inherited, are clinically and genetically heterogeneous. We describe the clinical and electrophysiological characteristics of an axonal autosomal recessive form of Charot-Marie-Tooth disease in a French family, associated with a new mutation of the ganglioside-induced differentiation-associated protein-1 gene (GDAP1). Two sisters, born to non-consanguineous parents, presented severe proximal and distal sensorimotor deficit, areflexia, pes cavus, scoliosis and vocal cord and diaphragm paralysis. They lost ambulation in the third decade and since then they have been wheelchair bound. Nerve conduction studies were consistent with an axonal neuropathy. Clinical and electrophysiological examination of their parents and their brother was normal. Genetic analysis revealed a homozygous thymidine deletion at nucleotide position 558 resulting in a frameshift at codon 186 and a stop codon at position 205. This axonal form of Charot-Marie-Tooth disease associated with a new GDAP1 mutation is recessively inherited and is characterized by a severe phenotype, since patients become wheelchair bound in the third decade, and present vocal cord and diaphram paralysis, which may be missed as they had no respiratory symptoms until the third decade.
authors.affiliation: Department of Neurology, CHU de Lille, Hôpital Roger Salengro, Service de Neurologie D, 59037 Lille Cedex, France. t-stojkovic@chru-lille.fr
authors.forename: Tanya
authors.initials: T
authors.lastname: Stojkovic
authors.forename: Philippe
authors.initials: P
authors.lastname: Latour
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Viet
authors.forename: Jérôme
authors.initials: J
authors.lastname: de Seze
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Hurtevent
authors.forename: Antoon
authors.initials: A
authors.lastname: Vandenberghe
authors.forename: P
authors.initials: P
authors.lastname: Vermersch
mesh_terms: D000328:Adult; D002607:Charcot-Marie-Tooth Disease / Q000150:complications* / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004558:Electric Stimulation / Q000379:methods; D005071:Evoked Potentials / Q000528:radiation effects; D005192:Family Health; D005260:Female; D005602:France; D006801:Humans; D009132:Muscles / Q000502:physiology / Q000528:radiation effects; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009431:Neural Conduction / Q000528:radiation effects; D011930:Reaction Time / Q000528:radiation effects; D012133:Respiratory Paralysis / Q000209:etiology*; D035781:Siblings; D013936:Thymidine / Q000235:genetics; D014826:Vocal Cord Paralysis / Q000209:etiology*
chemical_list: C118663:GDAP protein; D009419:Nerve Tissue Proteins; D013936:Thymidine