Are all the previously reported genetic variants in limb girdle muscular dystrophy genes pathogenic?

ABSTRACT: Hundreds of variants in autosomal genes associated with the limb girdle muscular dystrophies (LGMDs) have been reported as being causative. However, in most cases the proof of pathogenicity derives from their non-occurrence in hundreds of healthy controls and/or from segregation studies in small families. The limited statistics of the genetic variations in the general population may hamper a correct interpretation of the effect of variants on the protein. To clarify the meaning of low-frequency variants in LGMD genes, we have selected all variants described as causative in the Leiden Open Variation Database and the Human Gene Mutation Database. We have systematically searched for their frequency in the NHLBI GO Exome Sequencing Project (ESP) and in our internal database. Surprisingly, the

SUBMITTER: Di Fruscio G 

PROVIDER: S-EPMC4519526 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature