Low-level dystrophin expression attenuating the dystrophinopathy phenotype.

ABSTRACT: The reading frame rule suggests that Duchenne muscular dystrophy (DMD) results from DMD mutations causing an out-of-frame transcript, whereas the milder Becker muscular dystrophy results from mutations causing an in-frame transcript. However, predicted nonsense mutations may instead result in altered splicing and an in-frame transcript. Here we report a 10-year-old boy with a predicted nonsense mutation in exon 42 who had a 6-minute walk time of 157% of that of age matched DMD controls, characterized as intermediate muscular dystrophy. RNA sequencing analysis from a muscle biopsy revealed only 6.0-9.8% of DMD transcripts were in-frame, excluding exon 42, and immunoblot demonstrated only 3.2% dystrophin protein expression. Another potential genetic modifier noted was homozygosity for the pr

SUBMITTER: Waldrop MA 

PROVIDER: S-EPMC9460236 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature