title: Identification of novel GDAP1 mutations causing autosomal recessive Charcot-Marie-Tooth disease.
abstract: Mutations in the ganglioside-induced differentiation-associated protein 1 gene cause either autosomal recessive demyelinating Charcot-Marie-Tooth disease type 4A or autosomal recessive axonal Charcot-Marie-Tooth disease with vocal cord paresis. We sequenced the ganglioside-induced differentiation-associated protein 1 gene in 138 patients from 119 unrelated families diagnosed with either demyelinating or axonal autosomal recessive Charcot-Marie-Tooth disease. We detected six distinct mutant alleles in four families, four of which are novel. Electrophysiological studies show severely slowed motor nerve conduction velocities with severely reduced compound muscle action potentials. However, one patient had a normal conduction velocity in the ulnar nerve. Based on the electrophysiological tests, patients with ganglioside-induced differentiation-associated protein 1 mutations will therefore be classified as either axonal or demyelinating Charcot-Marie-Tooth disease. The neuropathological aspect shows a divergent pattern; nerve biopsies taken from two siblings at the same age and sharing the same ganglioside-induced differentiation-associated protein 1 gene mutation showed a dissimilar severity stage.
authors.affiliation: Molecular Genetics Department, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UIA), Universiteitsplein 1, B-2610, Antwerp, Belgium.
authors.forename: Nadia
authors.initials: N
authors.lastname: Ammar
authors.forename: Eva
authors.initials: E
authors.lastname: Nelis
authors.forename: Luciano
authors.initials: L
authors.lastname: Merlini
authors.forename: Nina
authors.initials: N
authors.lastname: Barisić
authors.forename: Rim
authors.initials: R
authors.lastname: Amouri
authors.forename: Chantal
authors.initials: C
authors.lastname: Ceuterick
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Martin
authors.forename: Vincent
authors.initials: V
authors.lastname: Timmerman
authors.forename: Fayçal
authors.initials: F
authors.lastname: Hentati
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
mesh_terms: D000483:Alleles; D001120:Arginine / Q000235:genetics; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology / Q000648:ultrastructure; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis; D003711:Demyelinating Diseases / Q000503:physiopathology; D004594:Electrophysiology; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005998:Glycine / Q000235:genetics; D006639:Histidine / Q000235:genetics; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009431:Neural Conduction; D010375:Pedigree; D010525:Peripheral Nerves / Q000648:ultrastructure; D017422:Sequence Analysis, DNA; D014364:Tryptophan / Q000235:genetics
chemical_list: C118663:GDAP protein; D009419:Nerve Tissue Proteins; D006639:Histidine; D014364:Tryptophan; D001120:Arginine; D003545:Cysteine; D005998:Glycine