Exonic mutations in the SLC12A3 gene cause exon skipping and premature termination in Gitelman syndrome.

ABSTRACT: A variety of genetic backgrounds cause the loss of function of thiazide-sensitive sodium chloride cotransporter, encoded by SLC12A3, responsible for the phenotypes in Gitelman syndrome. Recently, the phenomenon of exon skipping, in which exonic mutations result in abnormal splicing, has been associated with various diseases. Specifically, mutations in exonic splicing enhancer (ESE) sequences can promote exon skipping. Here, we used a bioinformatics program to analyze 88 missense mutations in the SLC12A3 gene and identify candidate mutations that may induce exon skipping. The three candidate mutations that reduced ESE scores the most were further investigated by minigene assay, and two (p.A356V and p.M672I) caused abnormal splicing in vitro. Furthermore, we identified the p.M672I (c.2016G>A

SUBMITTER: Takeuchi Y 

PROVIDER: S-EPMC4310649 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature