A novel dysferlin mutant pseudoexon bypassed with antisense oligonucleotides.

ABSTRACT:

Objective

Mutations in dysferlin (DYSF), a Ca(2+)-sensitive ferlin family protein important for membrane repair, vesicle trafficking, and T-tubule function, cause Miyoshi myopathy, limb-girdle muscular dystrophy type 2B, and distal myopathy. More than 330 pathogenic DYSF mutations have been identified within exons or near exon-intron junctions. In ~17% of patients who lack normal DYSF, only a single disease-causing mutation has been identified. We studied one family with one known mutant allele to identify both the second underlying genetic defect and potential therapeutic approaches.

Methods

We sequenced the full DYSF cDNA and investigated antisense oligonucleotides (AONs) as a tool to modify splicing of the mRNA transcripts in order to process out mutant sequences.

Resu

SUBMITTER: Dominov JA 

PROVIDER: S-EPMC4241797 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature