The human connexin32 gene is transcribed from two tissue-specific promoters

The connexin32 (cx32) gene codes for the gap junction protein found in liver, pancreas and nervous tissue. Recently mutations in the coding region of this gene have been associated with the dominant X-linked form of Charcot-Marie-Tooth (CMTX1) neuropathy. Since some CMTX1 patients show no mutations in their cx32 gene coding region, it was speculated that these patients carry mutations in the promoter region of the gene. This paper describes the organization of the human cx32 gene and its tissue-specific transcription. The gene consists of three exons that are alternatively spliced to produce mRNAs with different 5'-untranslated regions (UTRs). Transcription is initiated from two tissue-specific promoters. In liver and pancreas, promoter P1, located more than 8 kb upstream of the translation start codon, is used, and the transcript is processed to remove a large intron. In contrast, in nerve cells, transcription is initiated from promoter P2, located 497 bp upstream from the translation start codon, and the transcript is processed to remove a small 355-pb intron. The downstream exon, which includes the entire coding sequence, is shared by both mRNAs. CMTX1 patients with a normal cx32 coding region are expected to have mutations in this newly described promoter P2 rather than the known promoter P1.