ZASP基因突变所致肌原纤维病一家系报道及文献复习

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。

Case Report of A Family with Myoifbrillar Myopathy Caused byZASP Gene Mutation and Literature Review

Aim To explore the clinical, pathological genetic findings of a family with Z-disc alternatively spliced PDZ-domain containing protein (ZASP) myopathy.MethodsThe clinical features, muscle MRI presents and pathological ifndings of a family with distal myopathy was analyzed. Genomic DNA of the proband was extracted from peripheral blood and the next generation sequencing of target gene (including 58 myopathy genes) was performed to explore the mutation ofZASP gene. Sanger sequencing was performed in other members of the family to identify the mutation.ResultsThe proband was a middle age woman and she suffered progressive lower limbs weakness and atrophy at her age of 52 years old. And there were six other members suffered involvement of muscles out of 15 relatives in two generations. Four of them were the same generation of the proband and the clinical presents and physical exam features of them were similar to the proband. Two of them were the next generation of the proband and one of these two relatives suffered eye closure weakness. The other one just had a slightly higher CK level (199 U·L-1) without any symptom. Pathologically, rimmed vacuoles and alkaline substances were seen in the muscle ifbers. The deposited material were positive for desmin. Dense matter deposition could be found around Z disc.ZASP gene sequencing found a reported mutation, A147T (c.G439A).ConclusionThis was the ifrst case report ofZASP gene myopathy family in China.