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目的通过对ZASP基因突变所致肌原纤维病一家系报道及文献复习,了解该病的临床、病理及基因突变特点。方法分析1例远端肌病患者的临床、肌肉MRI及肌肉病理特点,并追踪其家系家族史。先证者外周血提取DNA,进行目标区序列捕获二代测序(含58个肌病相关基因),明确存在ZASP基因变异。对家系其他成员进行Sanger测序进一步明确及验证突变位点。结果先证者为中年女性,52岁起病,表现为进行性双下肢无力伴双腿变细。先证者家系2代15名中,除先证者外共6名存在肌肉受累,4名为先证者同代亲属,临床特点与先证者类似;2名为先证者下一代亲属,其中1名仅有闭目肌受累及肌酸激酶(CK)轻度升高(291 U·L-1),另1名仅有CK轻度升高(199 U·L-1)。先证者肌肉病理发现肌细胞内有异常嗜伊红物质沉积和镶边空泡形成,免疫组化染色可见肌纤维内desmin蛋白沉积。电镜下可见Z线附近致密颗粒沉积。目标区序列捕获二代测序及Sanger测序确定该家系致病基因为ZASP基因已报道错义突变p.A147T(c.G439A)。结论 ZASP基因突变所致的肌原纤维病家系为国内首次报道。
Objective To investigate the clinical, pathological and gene mutation characteristics of myofibrillar disease caused by mutation of ZASP gene in a pedigree and literature review. Methods Clinical, muscle MRI and muscle pathology in one patient with distal myopathy were analyzed and their family history was followed up. Peripheral blood of probands DNA extraction, the target region sequence capture second-generation sequencing (including 58 myopathy-related genes), a clear presence of ZASP gene variation. Sanger sequencing of other members of the pedigree further identified and validated the mutation sites. The results of probands middle-aged women, 52-year-old onset, manifested as progressive weakness in both lower extremities with thin legs. The proband family of 2 generations of 15, in addition to the proband were a total of 6 muscle involvement, 4 probands of the same generation relatives, clinical features and proband similar; 2 probands next generation relatives, One of them had only a slight increase in creatine kinase (CK) (291 U · L-1) and a mild increase in CK (199 U · L-1) in only one eye muscle. In the muscle pathology of the probands, abnormal eosinophilic deposits and striped vacuoles were found in the muscle cells. The expression of desmin protein in the myofibers was observed by immunohistochemical staining. Under the electron microscope, dense particles are deposited near Z line. Target region sequence capture second-generation sequencing and Sanger sequencing to determine the family of pathogenic genes as ZASP gene has been reported missense mutation p.A147T (c.G439A). Conclusion The family of myofibrillar diseases caused by the mutation of ZASP gene was first reported in China.