一个全面性癫痫伴热性惊厥附加症家系临床表型及GABRG2基因突变分析  

Analysis of the GABRG2 gene mutation in a Chinese family with generalized epilepsy with febrile seizures plus

作　　者：孙慧慧[1] 张月华[1] 刘晓燕[1] 马秀伟[1] 吴沪生[2] 许克铭[3] 戚豫[1] 吴希如[1] 

机构地区：[1]北京大学第一医院儿科,100034 [2]北京儿童医院儿科 [3]首都儿科研究所儿科

出　　处：《中华医学遗传学杂志》2008年第6期611-615,共5页Chinese Journal of Medical Genetics

基　　金：北京市自然科学基金（7072083）

摘　　要：目的分析并确定一个全面性癫痫伴热性惊厥附加症（generalized epilepsy with febrile seizures plus，GEFS＋）家系临床表型，并对其GABAA受体γ2亚单位基因（GABAA—receptor γ2 subunit，CABRG2）进行突变筛查及遗传特征分析。方法收集先证者及其家系成员临床资料及外周血DNA，采用聚合酶链反应和DNA直接测序的方法进行GABRG2基因突变筛查，确定基因突变的位点，分析基因型与表型的关系。结果该家系为典型GEFS＋家系，3代共有7例受累成员，临床表型1例为热性惊厥（febrile seizures，FS），6例为热性惊厥附加症（febrileseizuresplus，FS＋）。该家系先证者的GABRG2基因存在第9外显子的杂合无义突变c．1287G〉A（p．W390X），先证者之母和具有GEFS＋表型的其他家系成员均携带该基因突变，1例携带该突变的家系成员临床表型正常，外显率约为87．5％（7／8）。结论该GEFS＋家系GABRG2基因突变P．W390X为遗传性突变，家系符合常染色体显性遗传伴外显率不全。GABRG2基因突变也是中国GEFS＋家系的致病基因之一。Objective To identify the mutation of the GABAA-receptor 72 subunit gene （GABRG2） in a Chinese family with generalized epilepsy with febrile seizures plus （GEFS ＋ ） and analyze the genotype-phenotype correlations and its inheritance. Methods Genomic DNA was extracted from peripheral blood lymphocytes of the proband and other available members in the GEFS ＋ family. The coding regions and flanking intronic regions of the GABRG2 gene were screened for mutations using polymerase chain reaction （PCR） and direct DNA sequencing. Results There were 7 af- fected members in the three-generation family, in which one with febrile seizures （FS） and six with febrile seizures plus （FS＋）. This family was consistent with the diagnostic criteria of GEFS ＋ . The nonsense mutation c. 1287G 〉 A （p. W390X） in the GABRG2 gene was initially identified in the proband. Seven affected members （6 FS ＋ and 1 FS） and one unaffected member carried the mutation. The nonsense mutation c. 1287G 〉 A/p. W390X in the GABRG2 gene was co-segregated with the GEFS ＋ family. The penetrance rate was about 87.5 % （7/8）. Conclusion This GEFS ＋ family was consistent with autosomal dominant inheritance with incomplete penetrance. GABRG2 mutation is also a diseasecausing mutation in Chinese GEFS ＋ patients. The p. W390X mutation has not been reported previously.

关 键 词：全面性癫痫伴热性惊厥附加症 GABAA受体 突变 

分 类 号：R686[医药卫生—骨科学]