title: A novel mutation of GDAP1 associated with Charcot-Marie-Tooth disease in three Italian families: evidence for a founder effect.
abstract: BACKGROUND
  Mutations in a gene encoding a novel protein of unknown function-the ganglioside-induced differentiation-associated protein 1 gene (GDAP1)-are associated with the autosomal recessive Charcot-Marie-Tooth disease type 4A (CMT4A).
  
  
  OBJECTIVE
  To investigate the role of GDAP1 mutations in causing autosomal recessive neuropathies in an Italian population.
  
  
  RESULTS
  76 patients with severe early onset polyneuropathy and possible autosomal recessive inheritance were screened for mutations. A T>G transversion (c.347 T>G) at codon 116 (M116R) was detected in four affected subjects from three apparently unrelated families. All patients had early onset of disease with pronounced foot deformities and impaired walking. Neurophysiological studies showed an extremely variable expression. Sural nerve biopsies revealed signs of both de-remyelination and axonal impairment, the most prominent feature being a severe loss of larger fibres. Haplotype analysis of the GDAP1 locus demonstrated a common disease haplotype.
  
  
  CONCLUSIONS
  The association of the mutation with a common haplotype suggested a common ancestor.
authors.affiliation: Department of Neuroscience, Ophthalmology and Genetics, Section of Medical Genetics, University of Genova, c/o DIMI - Viale Benedetto XV, 6 16132 Genova, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Di Maria
authors.forename: R
authors.initials: R
authors.lastname: Gulli
authors.forename: P
authors.initials: P
authors.lastname: Balestra
authors.forename: D
authors.initials: D
authors.lastname: Cassandrini
authors.forename: S
authors.initials: S
authors.lastname: Pigullo
authors.forename: L
authors.initials: L
authors.lastname: Doria-Lamba
authors.forename: M
authors.initials: M
authors.lastname: Bado
authors.forename: A
authors.initials: A
authors.lastname: Schenone
authors.forename: F
authors.initials: F
authors.lastname: Ajmar
authors.forename: P
authors.initials: P
authors.lastname: Mandich
authors.forename: E
authors.initials: E
authors.lastname: Bellone
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004594:Electrophysiology; D005260:Female; D018703:Founder Effect; D006023:Glycoproteins; D006239:Haplotypes; D006801:Humans; D040582:Inheritance Patterns; D007558:Italy; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015398:Signal Transduction
chemical_list: C118663:GDAP protein; D006023:Glycoproteins; D009419:Nerve Tissue Proteins