title: Mutations in the connexin 32 gene in X-linked dominant Charcot-Marie-Tooth disease (CMTX1)
abstract: X-linked dominant Charcot-Marie-Tooth disease (CMTX1) is a peripheral neuropathy which maps to Xq13 and is flanked by the loci DXS106 (Xq11.2-q12) and DXS559 (Xq13.1). Contained within this interval of approximately 2-3Mb of DNA is the gene, connexin 32 (locus designation GJ beta 1). This gene encodes a gap junction protein which is expressed in large quantities within the liver and throughout a range of other mammalian tissues. We have sequenced the coding region of exon 2 of this gene from affected individuals in nine families with CMTX 1 and have found mutations which segregate with the disease in eight of these families. The mutations detected include missense point mutations at codons 15, 60, 63, 208, and 215, a nonsense point mutation at codon 220, deletions of one base in codon 72/3 producing a stop codon 12 codons down stream and a three base pair deletion which can be predicted to result in the loss of a single amino acid. These findings are consistent with the disease CMTX1 being the result of mutations affecting the gene connexin 32 (Cx32).
authors.affiliation: Department of Molecular and Cell Biology, University of Aberdeen, Medical School, UK.
authors.forename: N
authors.initials: N
authors.lastname: Fairweather
authors.forename: C
authors.initials: C
authors.lastname: Bell
authors.forename: S
authors.initials: S
authors.lastname: Cochrane
authors.forename: J
authors.initials: J
authors.lastname: Chelly
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: M L
authors.initials: ML
authors.lastname: Mostacciuolo
authors.forename: A P
authors.initials: AP
authors.lastname: Monaco
authors.forename: N E
authors.initials: NE
authors.lastname: Haites
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D002874:Chromosome Mapping; D003062:Codon / Q000235:genetics; D017630:Connexins / Q000737:chemistry / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D017384:Sequence Deletion; D014960:X Chromosome; D000097002:Gap Junction beta-1 Protein
chemical_list: D003062:Codon; D017630:Connexins; D004247:DNA; D000097002:Gap Junction beta-1 Protein