PIGS基因突变所致的发育性癫痫性脑病家系的临床表现及遗传学分析

Analysis of clinical features and genetic variants in a family with developmental and epileptic encephalopathy induced by PIGS gene mutation

目的总结和分析磷脂酰肌醇聚糖锚定生抑合成S类(PIGS)基因突变所致的发育性癫痫性脑病(DEE)家系中2名患儿的临床表型及遗传特点。方法收集2021—2022年因“反复抽搐”就诊于广东医科大学附属医院门诊的2例患儿的临床资料及家族史,提取患儿及其家系成员的外周血样,采用全外显子组测序技术筛查患者致病基因,对可疑致病突变进行Sanger测序验证。结果例1,女,姐姐(先证者),8岁;例2,女,妹妹,6岁。均为婴儿期起病,表现为频繁全面性强直阵挛发作,伴严重发育落后,查体均发现特殊面容(拱形眉、杏仁眼、眼距宽、鼻梁低平、长人中、宽舌)及肌张力低下,异常视频脑电图及头颅磁共振结果。基因检测均提示PIGS基因c.1141_1164dup(p.Asp381_Val388dup)纯合突变,Sanger验证父母为杂合突变,结合临床表型和基因检测结果,2例患儿确诊为DEE-95(PIGS基因突变),经联合抗癫痫加用维生素B6治疗后抽搐改善。结论PIGS基因纯合突变是DEE-95致病原因,全外显子组测序有重要诊断价值,抗癫痫联合治疗加用维生素B6可控制抽搐发作。

Objective To summarize and analyzes the clinical features and genetic variants of two children in a family with developmental and epileptic encephalopathy(DEE)induced by phosphatidylinositol glycan anchor biosynthesis,class S(PIGS)gene mutation.Methods Clinical data and family history of two patients visited the outpatient of the Affiliated Hospital of Guangdong Medical University due to“recurrent seizures”from 2021 to 2022 were collected,peripheral blood samples of patients and family members were extracted.Whole exome sequencing and Sanger sequencing were carried out to detect the potential mutation.Results Case 1,female,sister(witness),8 years old,case 2 female,sister,6 years old,all of them were infantile onset,presented with frequent generalized tonic-clonic seizures,accompanied by severe developmental lag,physical examination found special facial features(arched eyebrow,almond eyes,wide eye distance,low nose bridge,long middle,wide tongue)and hypotonia,abnormal video EEG and skull magnetic resonance imaging results.All genetic tests indicated homozygous mutation of PIGS gene c.1141_1164dup(P.SP381_val388dUP),and Sanger verified that the parents were heterozygous mutations.Combined with the clinical phenotype and genetic detection results,2 cases were confirmed as DEE-95(PIGS gene mutation).Convulsions improved after treatment with vitamin B6 and antiepileptic combination.Conclusion Homozygous mutation of PIGS gene is the cause of DEE95.Whole exome sequencing is of great value for the diagnosis of DEE-95.Most of the patients need combination therapy,which is effective with the addition of vitamin B6.