title: C-terminal truncated dystrophin identified in skeletal muscle of an asymptomatic boy with a novel nonsense mutation of the dystrophin gene.
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 the dystrophin gene.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunokicho, Chuo, Kobe 650-0017, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Suminaga
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeshima
authors.forename: Hiroko
authors.initials: H
authors.lastname: Wada
authors.forename: Mariko
authors.initials: M
authors.lastname: Yagi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
mesh_terms: D002648:Child; D018389:Codon, Nonsense; D003402:Creatine Kinase / Q000097:blood; D016189:Dystrophin / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000502:physiology*; D020388:Muscular Dystrophy, Duchenne / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D017434:Protein Structure, Tertiary
chemical_list: D018389:Codon, Nonsense; D016189:Dystrophin; D003402:Creatine Kinase