摘要
导致抗肌营养不良蛋白基因未成熟的终止密码子的突变也导致了骨骼肌抗肌营养不良蛋白的全部缺失, 结果出现严重的杜兴肌营养不良性肌营养失调症。这里,首次报道了在肌浆膜中由无义突变引起的一个C- 末端截断的抗肌营养不良蛋白的定位。由于血清肌氨酸激酶活性增强,1例无症状的8岁男孩接受了骨骼肌抗肌营养不良蛋白的检查。值得注意的是,在Mab抗C-
Mutations that cause premature stop codons in the dys-trophin gene lead to a complete loss of dystrophin from skeletalmuscle, 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 themuscle plasma membrane. An asymptomatic 8 - y - old boy was examined for dystrophin in skeletal muscle because of high serum ereatine 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.
