Clinical and molceulcar analyses of facioscpubhumeral muscular dystrophy

面肩肱骨肌营养不良症(FSHD)是一种常见的常染色体显性遗传的肌肉疾病。大多数患者在染色体4q35上存在D4Z4重复数目的缺失。D4Z4重复区域的体细胞/生殖系嵌合体可能是导致下一代FSHD患者的原因。我们对FSHD患者及其亲本进行了Southern杂交分析，发现约20%的双亲是体细胞花叶。等位基因缺失的细胞比例与发病年龄/临床严重程度无明显差异。令人惊讶的是，近一半缺失等位基因的父母没有表现出临床症状，这表明这种疾病的渗透率比之前认为的要低得多(Goto等人，2004年)。FSHD的临床特征即使在一个家庭内也是非常不同的。基于我们最初的FSHD临床数据库，我们对40例4q35非连锁FSHD患者进行了详细的分析。我们报道了FSHD包含临床和遗传变异的疾病，其他疾病如Becker肌营养不良症可以表现出与FSHD非常相似的临床特征(Yamanaka et al.，2004)。由于多种原因，使用Southern blotting进行FSHD的基因诊断非常复杂，需要开发一种简单的方法。建立了一种利用长片段聚合酶链式反应(Long-PCR)技术进行FSHD分子诊断的新方法。我们证实，95%的4q35连锁FSHD患者可以通过检测与D4Z4数量相对应的PCR产物来诊断(提交的论文)。

Facioscapulohumeral muscular dystrophy(FSHD) is a common muscular disorder with autosomal dominant inheritance. Most of the patients have a deletion of numbers of D4Z4 repeats on chromosome 4q35.Somatic/germline mosaicism of the D4Z4 repeated region is suggested to cause de novo patients with FSHD in the next generation. We performed southern blot analysis on the FSHD patients and their parents, and revealed that about 20% of the parents were somatic mosaic. There was no difference between the ratio of the cells with deleted allele and the age at onset/clinical severity. Surprisingly, nearly a half of the parents with a deleted allele showed no clinical symptoms, which suggest much more low penetration of this disease than previously thought (Goto et al.,2004).Clinical features of FSHD are quite variable even within a family. We analyzed in detail on 40 patients with 4q35-unlinked FSHD, based on our original clinical database for FSHD. We reported that FSHD contains clinically and genetically variable disorders, and other diseases such as Becker muscular dystrophy could show quite similar clinical features to FSHD (Yamanaka et al.,2004).For the several reasons, genetic diagnosis of FSHD using southern blotting is quite complicate, and to develop a simple method is needed. We developed a new method for the molecular diagnosis of FSHD by using long PCR method. We confirmed that 95% of 4q35-linked FSHD patients can be diagnosed to detect a PCR product corresponding to the number of D4Z4 (paper submitted).