Point mutations of the connexin32 (GJB1) gene in X-linked dominant Charcot-Marie-Tooth neuropathy

• Published in: Human molecular genetics Vol. 3; no. 2; p. 355
• Main Authors: Ionasescu, V, Searby, C, Ionasescu, R
• Format: Journal Article
• Language: English
• Published: England 01.02.1994
• Subjects: Amino Acid Sequence; Base Sequence; Charcot-Marie-Tooth Disease - genetics; Connexins - genetics; Female; Gap Junction beta-1 Protein; Genes; Genes, Dominant; Humans; Male; Molecular Sequence Data; Pedigree; Point Mutation; X Chromosome
• ISSN: 0964-6906
• DOI: 10.1093/hmg/3.2.355

Ten families with X-linked dominant CMT neuropathy (CMTX1) were screened for point mutations of the connexin32 (Cx32, GJB1) gene. Two families showed missense mutations, respectively an A-->G transition at amino acid 102 (glutamate to glycine) and a C-->T transition at amino acid 142 (arginine to tryptophan). Three families showed nonsense mutations, respectively a C-->T transition at amino acid 22 (arginine to stop) a G-->T transversion at amino acid 186 (glutamate to stop), and a T-->A transversion at amino acid 217 (cysteine to stop). Five CMTX1 neuropathy families showed no evidence of point mutations of the connexin32 coding sequence. These findings suggest that the CMTX1 neuropathy genotype is heterogeneous or the result of promoter mutations, 3'-untranslated region mutations or exon/intron splice site mutations. Four of the reported mutations created or destroyed restriction enzyme sites: a HaeIII restriction enzyme site was destroyed by the mutation at amino acid position 22, a HpaII site was eliminated at amino acid position 142, a Bfal restriction site was created by the mutation at amino acid 186 and a Ddel restriction site was created by the mutation at amino acid 217. These changes allowed us to test family members for the mutations and observe the segregation of the disease with the mutations.