RGD Reference Report - Genomic organization of the human muscle chloride channel CIC-1 and analysis of novel mutations leading to Becker-type myotonia. - Rat Genome Database

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Genomic organization of the human muscle chloride channel CIC-1 and analysis of novel mutations leading to Becker-type myotonia.

Authors: Lorenz, C  Meyer-Kleine, C  Steinmeyer, K  Koch, MC  Jentsch, TJ 
Citation: Lorenz C, etal., Hum Mol Genet 1994 Jun;3(6):941-6.
RGD ID: 704389
Pubmed: (View Article at PubMed) PMID:7951242

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.

Annotation

Disease Annotations    
myotonia congenita  (IAGP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Clcn1  (chloride voltage-gated channel 1)

Genes (Mus musculus)
Clcn1  (chloride channel, voltage-sensitive 1)

Genes (Homo sapiens)
CLCN1  (chloride voltage-gated channel 1)


Additional Information