Genomic organization of the human muscle chloride channel CIC-1 and analysis of novel mutations leading to Becker-type myotonia.
The muscle chloride channel CIC-1 regulates the electric excitability of the skeletal muscle membrane. Mutations in the gene encoding this chloride channel ( CLCN1) are responsible for both human purely myotonic disorders, autosomal recessive generalized myotonia (Becker's disease, GM) and autosomal dominant myotonia congenita (Thomsen's disease, MC). We now show that the protein-coding sequence of the CLCN1 gene is organized into 23 exons. The CIC-1 upstream region contains a canonical TATA box, several consensus binding sites for myogenic transcription factors and two other putative regulatory elements. SSCA analysis of a German GM family revealed that affected members are compound heterozygotes having two novel mutations. G979A affects a splice consensus site at the end of exon 8, and G1488T in exon 14 leads to a replacement of a positive charge in a highly conserved putative transmembrane domain (R496S). Functional expression of R496S cRNA in Xenopus oocytes did not yield detectable currents. It neither suppressed wild-type currents in a co-expression assay, confirming it as a recessive mutation.[1]References
- Genomic organization of the human muscle chloride channel CIC-1 and analysis of novel mutations leading to Becker-type myotonia. Lorenz, C., Meyer-Kleine, C., Steinmeyer, K., Koch, M.C., Jentsch, T.J. Hum. Mol. Genet. (1994) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
