title: Mutations in GDAP1: autosomal recessive CMT with demyelination and axonopathy.
abstract: BACKGROUND
  Mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) were recently shown to be responsible for autosomal recessive (AR) demyelinating Charcot-Marie-Tooth disease (CMT) type 4A (CMT4A) as well as AR axonal CMT with vocal cord paralysis.
  
  
  METHODS
  The coding region of GDAP1 was screened for the presence of mutations in seven families with AR CMT in which the patients were homozygous for markers of the CMT4A locus at chromosome 8q21.1.
  
  
  RESULTS
  A nonsense mutation was detected in exon 5 (c.581C>G, S194X), a 1-bp deletion in exon 6 (c.786delG, G262fsX284), and a missense mutation in exon 6 (c.844C>T, R282C).
  
  
  CONCLUSIONS
  Mutations in GDAP1 are a frequent cause of AR CMT. They result in an early-onset, severe clinical phenotype. The range of nerve conduction velocities (NCV) is variable. Some patients have normal or near normal NCV, suggesting an axonal neuropathy, whereas others have severely slowed NCV compatible with demyelination. The peripheral nerve biopsy findings are equally variable and show features of demyelination and axonal degeneration.
authors.affiliation: Molecular Genetics Department, Flanders Interuniversity Institute of Biotechnology, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Nelis
authors.forename: S
authors.initials: S
authors.lastname: Erdem
authors.forename: P Y K
authors.initials: PY
authors.lastname: Van Den Bergh
authors.forename: M-C
authors.initials: MC
authors.lastname: Belpaire-Dethiou
authors.forename: C
authors.initials: C
authors.lastname: Ceuterick
authors.forename: V
authors.initials: V
authors.lastname: Van Gerwen
authors.forename: A
authors.initials: A
authors.lastname: Cuesta
authors.forename: L
authors.initials: L
authors.lastname: Pedrola
authors.forename: F
authors.initials: F
authors.lastname: Palau
authors.forename: A A W M
authors.initials: AA
authors.lastname: Gabreëls-Festen
authors.forename: C
authors.initials: C
authors.lastname: Verellen
authors.forename: E
authors.initials: E
authors.lastname: Tan
authors.forename: M
authors.initials: M
authors.lastname: Demirci
authors.forename: C
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: P
authors.initials: P
authors.lastname: De Jonghe
authors.forename: H
authors.initials: H
authors.lastname: Topaloglu
authors.forename: V
authors.initials: V
authors.lastname: Timmerman
mesh_terms: D017668:Age of Onset; D001369:Axons / Q000473:pathology*; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D003711:Demyelinating Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D004594:Electrophysiology; D005190:Family; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009431:Neural Conduction / Q000502:physiology; D010375:Pedigree; D013497:Sural Nerve / Q000473:pathology; D014421:Turkey
chemical_list: C118663:GDAP protein; D009419:Nerve Tissue Proteins