Mutations in the connexin 32 gene in X-linked dominant Charcot-Marie-Tooth disease (CMTX1)

Journal article

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: Fairweather, N; Bell, C; Cochrane, S; Chelly, J; Wang, S

• Publication status: Published
• Journal: Human molecular genetics
• Volume: 3
• Issue: 1
• Pages: 29-34
• Publication date: 1994-01-01
• DOI: 10.1093/hmg/3.1.29
• EISSN: 1460-2083
• ISSN: 0964-6906
• Language: English
• Keywords: Molecular Sequence Data; DNA; Sequence Deletion; X Chromosome; Exons; Connexins; Protein Structure, Secondary; Codon; Female; Male; Charcot-Marie-Tooth Disease; Humans; Amino Acid Sequence; Polymerase Chain Reaction; Point Mutation; Chromosome Mapping; Pedigree; Base Sequence