Exon skipping induced by nonsense/frameshift mutations in DMD gene results in Becker muscular dystrophy

This study aims to find BMD cases with nonsense/frameshift mutations inDMD and to investigate the exon skipping rate of those nonsense/frameshift mutations. We searched for BMD cases with nonsense/frameshift mutations inDMD in the Japanese Registry of Muscular Dystrophy. For eachDMD mutation identified, we constructed minigene plasmids containing one exon with/without a mutation and its flanking intronic sequence. We then introduced them into HeLa cells and measured the skipping rate of transcripts of the minigene by RT-qPCR. We found 363 cases with a nonsense/frameshift mutation inDMD gene from a total of 1497 dystrophinopathy cases in the registry. Among them, 14 had BMD phenotype. Exon skipping rates were well correlated with presence or absence of dystrophin, suggesting that 5% exon skipping rate is critical for the presence of dystrophin in the sarcolemma, leading to milder phenotypes. Accurate quantification of the skipping rate is important in understanding the exact functions of the nonsense/frameshift mutations inDMD and for interpreting the phenotypes of the BMD patients.
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research