title: Two novel connexin32 mutations cause early onset X-linked Charcot-Marie-Tooth disease.
abstract: BACKGROUND
  X-linked Charcot-Marie Tooth (CMT) is caused by mutations in the connexin32 gene that encodes a polypeptide which is arranged in hexameric array and form gap junctions.
  
  
  METHODS
  We describe two novel mutations in the connexin32 gene in two Norwegian families.
  
  
  RESULTS
  Family 1 had a c.225delG (R75fsX83) which causes a frameshift and premature stop codon at position 247. This probably results in a shorter non-functional protein structure. Affected individuals had an early age at onset usually in the first decade. The symptoms were more severe in men than women. All had severe muscle weakness in the legs. Several abortions were observed in this family. Family 2 had a c.536 G>A (C179Y) transition which causes a change of the highly conserved cysteine residue, i.e. disruption of at least one of three disulfide bridges. The mean age at onset was in the first decade. Muscle wasting was severe and correlated with muscle weakness in legs. The men and one woman also had symptom from their hands. The neuropathy is demyelinating and the nerve conduction velocities were in the intermediate range (25-49 m/s). Affected individuals had symmetrical clinical findings, while the neurophysiology revealed minor asymmetrical findings in nerve conduction velocity in 6 of 10 affected individuals.
  
  
  CONCLUSIONS
  The two novel mutations in the connexin32 gene are more severe than the majority of previously described mutations possibly due to the severe structural change of the gap junction they encode.
authors.affiliation: Faculty Division Akershus University Hospital, University of Oslo, 1474 Nordbyhagen, Oslo, Norway. g.j.braathen@medisin.uio.no
authors.forename: Geir J
authors.initials: GJ
authors.lastname: Braathen
authors.forename: Jette C
authors.initials: JC
authors.lastname: Sand
authors.forename: Geir
authors.initials: G
authors.lastname: Bukholm
authors.forename: Michael B
authors.initials: MB
authors.lastname: Russell
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D017630:Connexins / Q000235:genetics*; D005260:Female; D017629:Gap Junctions / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D012720:Severity of Illness Index; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D000097002:Gap Junction beta-1 Protein