良性家族性新生儿惊厥 KCNQ2 基因新突变

目的 对一个中国良性家族性新生儿惊厥(benign familial neonatal convulsions，BFNC)家系进行基因诊断，并探讨其分子发病机理。方法 对该家系进行详细的临床检查及疾病基因的连锁分析。应用聚合酶链反应(polymerase chain reaction，PCR)-DNA直接测序，并用PCR-单链构象多态(single strand conformation polymorphism，SSCP)对先证者、家系内16人及家系外72名无血缘关系的正常入进行KCNQ2基因突变分析。结果 连锁分析提示该家系与KCNQ2基因连锁，并排除与KCNQ3基因连锁。PCR—DNA直接测序在先证者发现．KCNQ2基因突变193ldelG，PCR—SSCP发现家系内其他患者均出现与先证者相同的异常SSCP条带，而72名正常人未出现此异常条带。结论 KCNQ2基因突变是中国人BFNC的发病原因之一，193ldelG是国内外未曾报道过的新突变，连锁分析结合基因突变分析可对BFNC患者进行基因诊断。

A novel mutation of KCNQ2 gene in a Chinese family with benign familial neonatal convulsions

Objective To diagnose a Chinese benign familial neonatal convulsions (BFNC) family at the level of gene and investigate its molecular pathogenesis. Methods All family members were studied by clinical examinations and linkage analysis. Mutation analysis of KCNQ2 gene was made by means of polymerse chain reaction (PCR)-direct secquencing and PCR-single strand conformation polymorphism (SSCP) in the proband, 16 family members and 72 unrelated normal individuals. Results Linkage analysis hinted the linkage of BFNC toKCNQ2, while the linkage toKCNQ3 was excluded. Mutation 1931delG ofKCNQ2 gene was found in the proband by DNA-direct sequencing. The same SSCP variant as the proband's was showed in the rest affected members of this family but not in the unaffected members of this family and all of the 72 unrelated normal individuals. Conclusion 1931delG ofKCNQ2 gene can cause BFNC in China and is novel mutation. The combination of linkage analysis and gene analysis is useful for gene diagnosis.