摘要目的 总结1例脊髓性肌萎缩症伴进行性肌阵挛癫痫(SMA-PME)患儿的临床及遗传学特征,并进行文献复习.方法 对2016年8月就诊于北京大学第一医院儿科的1例SMA-PME患儿的临床及基因检测进行分析,并对至今共报道的10例ASAH1基因突变确诊病例进行汇总分析.结果 患儿,女,4岁.1岁2个月时能独立行走,之后缓慢出现进行性行走困难,3岁9个月时出现频繁身体抖动甚至摔倒,偶有愣神表现.全外显子组基因测序结果示患儿携带ASAH1基因复合杂合突变:第4外显子c.256_c.257insA(p.T86Nfs*14)杂合移码突变和第4外显子c.125C>T(p.T42M)杂合错义突变,该移码突变为国际上尚未报道的新突变,其父携带c.256_c.257insA突变,其母携带c.125C>T突变.患儿自起病以来,运动功能进行性倒退,智力基本正常.至2016年10月,国外共报道10例确诊病例,结合本例汇总分析显示,所有病例均有肌无力及癫痫发作,且多以肌无力起病,其次可出现震颤、吞咽困难、反复肺炎等表现.共发现ASAH1基因8种不同的突变位点,其中c.125C>T最常见,均符合常染色体隐性遗传.所有病例早期发育里程碑基本正常,病程中部分患儿认知损害不明显,文献报道时已有4例死亡(13~19岁).结论 SMA-PME为一种少见的进行性常染色体隐性遗传病,由ASAH1基因突变所致,本例携带1个文献报道的最常见位点及1个未报道的移码突变位点,为中国首例基因确诊的SMA-PME病例.

abstractsObjective To investigate the clinical and genetic features of a Chinese child with spinal muscular atrophy with progressive myoclonic epilepsy(SMA-PME)and review the related literatures.Methods The clinical and genetic data of 1 patient with SMA-PME,who had visited the Department of Pediatrics,Peking University First Hospital in August 2016,were analyzed.The clinical and genetic features of 10 reported ASAH1-related cases and this case were reviewed.Results The patient was a girl aged 4 years.At the age of 1 year and 2 months,she was able to walk independently and then started to show slowly progressive difficulty in walking.At age 3 years and 9 months,she developed frequent myoclonic jerks of trunk or even falls,and had occasional staring.The patient was revealed to have compound heterozygous mutations in ASAH1 gene,c.256_c.257insA(p.T86Nfs*14)inherited from her father and c.125C>T(p.T42M)inherited from her mother.The mutation p.T86Nfs*14 was not reported before.Since the onset of the disease,her motor skills were progressive impaired but intelligence was basically normal.A total of 10 ASAH1-related cases were reported until October 2016.By analyzing the data of the 10 foreign cases and this case,muscular weakness and seizures were presented in all cases.Onset usually with muscular weakness,other symptoms including tremor,dysphagia and recurrent pneumonia etc.The total 8 mutations were found and the most frequent mutation was c.125C>T.The mode of inheritance all conformed to autosomal recessive.In all cases,early developmental milestones were normal,and no obvious cognitive impairment were found during the course of the disease in some of them.Four ca-ses were dead at the age of 13 to 19 years in the literatures.Conclusion SMA-PME is a rare autosomal recessive disease associated with mutations of ASAH1 gene.The patient is the first Chinese case of SMA -PME confirmed by ASAH1 gene mutations that including a common mutation and a novel frame shift mutation.