C-terminal truncated dystrophin identified in skeletal muscle of an asymptomatic boy with a novel nonsense mutation of the dystrophin gene

Pediatric Research
Ryo SuminagaMasafumi Matsuo

Abstract

Mutations that cause premature stop codons in the dystrophin gene lead to a complete loss of dystrophin from skeletal muscle, resulting in severe Duchenne muscular dystrophy. Here, a C-terminally truncated dystrophin resulting from a novel nonsense mutation is shown for the first time to be localized to the muscle plasma membrane. An asymptomatic 8-y-old boy was examined for dystrophin in skeletal muscle because of high serum creatine kinase activity. Remarkably, no dystrophin labeling was seen with an MAb against the C-terminal domain, suggesting the presence of an early stop codon in the dystrophin gene. Labeling with an antibody specific to the N-terminal domain, however, revealed weak, patchy, and discontinuous staining, suggesting limited production of a truncated form of the protein. Molecular analysis revealed a novel nonsense mutation (Q3625X) as a result of a single nucleotide change in the patient's genomic DNA (C10873T), leaving 1.6% of dystrophin gene product unsynthesized at the C terminus. Dystrophin mRNA analysis did not show rescue of the nonsense mutation as a result of exon-skipping by an alternative splicing mechanism. This is the first report of an asymptomatic dystrophinopathy with a nonsense mutation in th...Continue Reading

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Citations

Aug 4, 2005·European Journal of Human Genetics : EJHG·Sylvie Tuffery-GiraudMireille Claustres
Apr 24, 2008·Brain & Development·Shigemi KimuraTeruhisa Miike
Aug 5, 2006·Clinical Chemistry·Roger D KleinAllen E Bale

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