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CABAA受体γ2哑单化基因(GABAA-receptor γ2 subunit,GABRG2)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GBRG2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(febrile seizures plus,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GEPS+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GBRG2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小全.GABRG2基因突变也是中国GEFS+家系的致病基因之一.

abstractsObjective To identify the mutation of the GABAA-receptor γ2 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 GABR2 gene were screened for mutations using polymerase chain reaction (PCR) and direct DNA sequencing.Results There were 7 affected 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 carded the mutation.The nonsense mutation c.1287G＞A/p.W390X in the GABRG2 gene was co-segregated withtheGEFS+ 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.