PCDH19基因变异相关癫痫家系的临床特点及遗传学分析  

Clinical and genetic analysis of patients of PCDH19 gene related epilepsy

作　　者：张君[1] 杨志刚[1] 刘淼[1] 王营 王媛[1] 陈国洪 马燕丽 张文乾[1] 毕文静 邓劼[2] 王芳 Zhang Jun;Yang Zhigang;Liu Miao;Wang Ying;Wang Yuan;Chen Guohong;Ma Yanli;Zhang Wenqian;Bi Wenjing;Deng Jie;Wang Fang(Department of Neurology,Children′s Hospital Affiliated to Zhengzhou University,Zhengzhou 450018,China;Department of Neurology,Beijing Children′s Hospital,Capital Medical University,Beijing 100045,China;Department of Pediatrics,Zhoukou Children′s Hospital,Zhoukou 466000,China)

机构地区：[1]郑州大学附属儿童医院神经内科,郑州450018 [2]首都医科大学附属北京儿童医院神经内科,北京100045 [3]周口市儿童医院儿科,周口466000

出　　处：《中华神经科杂志》2024年第10期1120-1126,共7页Chinese Journal of Neurology

基　　金：河南省医学科技攻关计划联合共建项目(LHGJ20230597)。

摘　　要：目的分析探讨PCDH19基因变异相关癫痫家系的临床及基因变异特点,提高对该病的早期认识。方法收集2018年10月至2023年8月于郑州大学附属儿童医院神经内科确诊的3例PCDH19基因变异相关癫痫先证者资料,同时收集分析其各自来源3个家系的临床资料和基因检测结果。结果3例PCDH19基因变异相关癫痫患儿均为女性,且婴儿期起病,病初主要临床表现均为热敏感和丛集性癫痫发作,且单药不易控制。例1经服用两种抗发作药物无抽搐发作,智力较正常同龄儿童稍落后;例2多种抗发作药物联合应用仍间断抽搐发作,智力明显落后于同龄儿;例3经两种抗发作药物联合应用无抽搐发作,目前智力发育基本正常。基因检测结果显示:先证者1 PCDH19基因发现新发错义c.369C>G杂合变异,先证者2 PCDH19基因发现母源性错义c.1652T>A杂合变异,先证者3 PCDH19基因发现父源性错义c.278G>A杂合变异,3个变异既往均未见报道。结论PCDH19基因变异相关癫痫是一种特殊的X连锁遗传方式的癫痫综合征,具有热敏感和丛集性发作的特点,基因检测有助于早期诊断,尽早形成科学合理的临床方案。3个变异(c.369C>G、c.1652T>A、c.278G>A)丰富了PCDH19基因变异谱。ObjectiveTo investigate the clinical and gene variant characteristics of PCDH19 gene related epilepsy,and improve the ability of clinicians in early disease identification.MethodsThe clinical data of 3 PCDH19 gene related epilepsy patients admitted to Children′s Hospital Affiliated to Zhengzhou University from October 2018 to August 2023 diagnosed by gene detection were reviewed and analyzed.ResultsAll the patients are female,and the onset age of seizure ranged in their infancy.Seizures in clusters and fever sensitivity were observed in all patients,and were very hard to control by single-drug treatment.Proband 1 was seizure-free after 2 kinds of anti-epileptic drug treatment,but with mild degree of intellectual disability.Proband 2 had refractory epilepsy with severe degree of intellectual disability.Proband 3 was seizure-free after 2 kinds of anti-epileptic drug treatment and without intellectual disability.In the first family,the proband carried heterozygous c.369C>G variant in the PCDH19 gene which was identified as de novo after parental validation.In the second family,the proband carried c.1652T>A variant inherited from her mother.In the third family,the proband carried c.278G>A variant inherited from her father.The 3 mutations had not been reported in the Human Gene Mutation Database.Conclusions PCDH19 gene related epilepsy is one special kind of X-linked inherited epilepsy syndrome characterized by seizures in clusters and sensitivity to fever.And gene detection can help with early diagnosis and make rational clinical strategies in time.The variants c.369C>G,c.1652T>A and c.278G>A have enriched the gene variant spectrum of PCDH19.

关 键 词：癫痫 发作 突变 PCDH19基因 

分 类 号：R742.1[医药卫生—神经病学与精神病学]