ClC1 chloride channel in myotonic dystrophy type 2 and ClC1 splicing in vitro.

ABSTRACT: Myotonic dystrophy type 2 (DM2) is caused by CCTG-repeat expansions. Occurrence of splicing and mutations in the muscle chloride channel gene CLCN1 have been reported to contribute to the phenotype. To examine the effect of CLCN1 in DM2 in Germany, we determined the frequency of a representative ClC1 mutation, R894X, and its effect on DM2 clinical features. Then, we examined CLCN1 mRNA splice variants in patient muscle functionally expressed the most abundant variant, and determined its subcellular localization. Finally, we established a cellular system for studying mouse clcn1 pre-mRNA splicing and tested effects of expression of (CCUG)₁₈, (CUG)₂₄ and (AAG)₂₄ RNAs. The R894X mutation was present in 7.7% of DM2 families. DM2 R894X-carriers had more myotonia and myalgia than non-carriers. T

SUBMITTER: Ursu SF 

PROVIDER: S-EPMC3476861 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature