Novel mutations at carboxyl terminus of CIC‐1 channel in myotonia congenita

Objectives –  Myotonia congenita (MC), caused by mutations in the muscle chloride channel ( CLCN1 ) gene, can be inherited dominantly or recessively. The mutations at the carboxyl terminus of the CLCN1 gene have been identified in MC patients, but the functional implication of these mutations is unknown. Material and methods –  Direct sequencing of polymerase chain reaction products covering the whole coding region of the CLCN1 gene was performed in a MC family. This study was designed to investigate the clinical manifestations and genetic analysis of the CLCN1 gene. Results –  We identified two novel mutations, 2330delG and 1892C>T, from a genetic screening of the CLCN1 gene in the MC family. The 2330delG mutant allele producing a fs793X truncated protein was identified in a heterozygous state in all the patients. The 1892C>T nucleotide change induced a missense mutation (T631I) found in several asymptomatic individuals, indicating that it may not be associated with MC. Intriguingly, the 2330delG mutation was also found in an asymptomatic subject who also carried the 1892C>T mutation. Conclusion –  The data indicate that the fs793X mutant protein causes dominantly inherited MC. Because the mutation has been found in a recessive pedigree, the fs793X mutation may have a dual inheritance pattern.