部分性癫(癎)伴热性惊厥附加症家系中的SCN1A基因嵌合突变

目的 筛查一个部分性癫伴热性惊厥附加症(partial epilepsy with febrile seizures plus,PEFS+)家系中的钠通道α1基因(voltage-gated sodium channel α1-subunit,SCN1A)及其遗传特性.方法 总结一个PEFS+家系中2例患者及其父亲的临床特点,应用变性高效液相色谱(denaturing high performance liquid chromtography,DHPLC)技术筛查SCN1A全部26个外显子,发现有异常洗脱峰者进行直接测序,对直接测序未能证实突变的再进行焦磷酸测序.结果 先证者及其同父异母姐姐均为PEPS+患者,他们在SCN1A基因第26号外显子发现有相同的杂合突变A5768G,并导致编码的氨基酸改变Q1923R,其父亲儿时频繁出现热性惊厥(febrile seizures,FS),后自然痊愈,直接测序未发现异常,进一步用焦磷酸测序则发现该位点存在嵌合突变(突变量为25%).结论 SCN1A基因突变可导致部分性癫.PEFS+可遗传,而携带致病基因者可因体内发生嵌合突变,致病基因含量偏低导致临床症状轻微.

Mosaic SCN1A mutation in a family with partial epilepsy with febrile seizures plus

Objective To study the SCN1A gene in a family with partial epilepsy with febrile seizures plus ( PEFS+ ) and its characteristics of inheritance. Methods The clinical features of the 2 patients and their father were summarized. All 26 exons of SCN1A gene were screened with denaturing high performance liquid chromatography (DHPLC), and direct sequence analysis was pedormed on those with abnormal elution peak. Pyrosequencing was subsequently performed in those without abnormality in direct sequence analysis. Results The proband and his sister had the phenotype of PEFS+ . The same heterozygous mutations (AS768G) on exon 26 which caused the related amino acid change (Q1923R) were found among them. Their father had frequent febrile seizures (FS) in childhood, and seizures stopped spontaneously. No abnormality was found in direct sequence but mosaic mutation in the same site was discovered with pyrosequencing (mutation quantity was 25% ). Conclusions The mutatin of SCN1A could cause partial epilepsy. PEFS+ could be inherited, the relatives carrying the affected gene may have mild clinical symptoms, possibly resulting from the low concentration of the mutated gene due to mosaic mutation.