PDF(Pubmed)
Abstract：
We present the case of a male patient who was ultimately diagnosed with Becker muscular dystrophy (BMD; MIM# 300376) after the onset of muscle weakness in his teens progressively led to significant walking difficulties in his twenties. A genetic diagnosis was pursued but initial investigation revealed no aberrations in the dystrophin gene (DMD), although immunohistochemistry and Western blot analysis suggested the diagnosis of dystrophinopathy. Eventually, after more than 10 years, an RNA analysis captured abnormal splicing where 154 nucleotides from intron 43 were inserted between exon 43 and 44 resulting in a frameshift and a premature stop codon. Normal splicing of the DMD gene was also observed. Additionally, a novel variant c.6291-13537A>G in DMD was confirmed in the genomic DNA of the patient. The predicted function of the variant aligns with the mRNA results. To conclude, we here demonstrate that mRNA analysis can guide the diagnosis of non-coding genetic variants in DMD.
摘要：
我们介绍了一名男性患者的情况，该患者在十几岁的肌肉无力发作后，最终被诊断出患有Becker肌营养不良症（BMD；MIM＃300376），逐渐导致二十多岁的严重行走困难。进行了基因诊断，但初步调查显示肌营养不良蛋白基因（DMD）没有异常，尽管免疫组织化学和Westernblot分析提示诊断为肌萎缩蛋白病。最终,十多年后，RNA分析捕获了异常剪接,其中来自内含子43的154个核苷酸插入外显子43和44之间,导致移码和提前终止密码子。还观察到DMD基因的正常剪接。此外,在患者的基因组DNA中证实了DMD中的新变体c.6291-13537A>G。变体的预测功能与mRNA结果比对。最后，我们在此证明mRNA分析可以指导DMD非编码遗传变异的诊断.
