多发先天性畸形-肌张力低下-癫痫综合征1一例并文献复习  

Multiple congenital anomalies-hypotonia-seizures syndrome 1： case report and review of literature

作　　者：胥雨菲 李牛[1] 李国强[1] 王秀敏[2] 周云芳[3] 殷蕾[3] 王剑[1] Xu Yufei Li Niu Li Guoqiang Wang Xiumin Zhou Yunfang Yin Lei Wang Jian(Department of Medical Genetics ＆ Molecular Diagnostic Laboratory, Shanghai Children＇s Medical Center, Affiliated Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China)

机构地区：[1]上海交通大学医学院附属上海儿童医学中心医学遗传科,200127 [2]上海交通大学医学院附属上海儿童医学中心内分泌遗传代谢科,200127 [3]上海交通大学医学院附属上海儿童医学中心罕见疑难病门诊,200127

出　　处：《中华儿科杂志》2017年第3期215-219,共5页Chinese Journal of Pediatrics

基　　金：上海市科委国际合作项目（15410722800）

摘　　要：目的 对多发先天性畸形-肌张力低下-癫痫综合征1（MCAHS l）的临床表型及基因变异特征进行分析.方法 总结上海儿童医学中心2015年12月确诊的1例MCAHS 1患儿的临床资料、实验室检查,并提取患儿及其父母外周血DNA,采用靶向基因高通量测序技术检测与患儿症状相关的致病基因,应用Sanger测序进行验证.以“PIGN gene”为关键词,在Pubmed、Embase数据库中检索建库至2017年1月以来的相关文献,复习PIGN基因变异相关疾病的临床表现、检查结果及预后.结果 患儿男,3月龄16 d,以“生后20 d始反复抽搐”为主要症状,伴肌张力低下、发育迟缓,常规血液学、生化、代谢检测及影像学检查未见明显异常,其兄8月龄始反复抽搐发作,至20月龄死亡.基因检测发现患儿存在PIGN基因的复合杂合变异,一个为剪接位点变异（c.963G＞A,第8外显子最后一位）,为已报道变异位点;另一变异为无义变异（c.2773A＞T,p.Lys925＊）,尚未见报道.两个变异位点分别来源于患儿的父亲及母亲.检索到人类PIGN变异所致疾病的相关报道9篇,国内尚未见相关病例报道.包括本例,一共22例病例,临床表现以发育迟缓、肌张力低下、癫痫最为多见;基因变异以错义变异最常见;预后不佳,8例死亡,余患儿表现为不同程度难治性癫痫、严重精神发育迟滞、肌无力.结论 MCAHS 1临床表现为癫痫、严重发育迟缓、肌张力低下,可能伴有其他器官、系统的多发畸形.PIGN基因纯合变异或复合杂合变异是其致病原因.Objective To analyze and summarize the clinical and molecular characteristics of the patients with multiple congenital anomalies-hypotonia-seizures syndrome 1 （MCAHS 1）.Method Clinical data and test results were collected from a patient who was diagnosed with confirmed genetic basis of MCAHS 1 in Shanghai Children＇s Medical Center since December 2015.The patient and his parents were examined by the next generation sequencing （NGS） technology using peripheral blood genomic DNA,and the relevant mutations identified by NGS were verified with Sanger sequencing.Related literature was searched from PubMed and Embase databases （from their establishment to January 2017） by using ＂PIGN gene＂ as a keyword,the retrieved articles were further reviewed for the clinical manifestations,results and prognosis of PIGN related variants.Result A nearly 4-month-old Chinese boy was presented with epilepsy,hypotonia,developmental delay,accompanied by nearly normal laboratory test results.The NGS analysis revealed a compound heterozygous variations in the PIGN gene,included a known splice site mutation （c.963G 〉 A） which was inherited from his father,and a novel nonsense mutation （c.2773A 〉 T,p.Lys925 ＊） which was inherited from his mother.Nine associated articles were retrieved.Including our patient,a total of 22 cases were identified as the PIGN variants.The most common clinical manifestations were developmental delay,hypotonia,and epilepsy.Missense varients were most frequently found.Prognosis was poor.Eight cases died,while survived cased suffered from refractory epilepsy,profound mental retardation,muscle weakness,etc.Conclusion MCAHS1 is characterized by epilepsy,severe developmental delay,hypotonia,and may be accompanied by multiple malformations of other systems.Homozygous or compound heterozygous variants in PIGN gene are the cause of the disease.

关 键 词：多发先天性畸形-肌张力低下-癫痫综合征 糖基磷脂酰肌醇类 基因 高通量核苷酸测序 

分 类 号：R725.9[医药卫生—儿科] R742.1[医药卫生—临床医学]