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目的分析电压门控钾离子通道基因KCNQ2与1个良性家族性婴儿惊厥(benign familial infantile convulsions,BFIC)家系的关系,探讨BFIC的分子遗传机制。方法1个中国陕西地区4代BFIC家系,采集41名家系成员及家系外75名健康对照的血样,采用PCR扩增、DNA直接测序技术进行KCNQ2基因突变分析,采用多聚酶链反应-单链构象多态性进行基因型和表型共分离研究。结果PCR-DNA直接测序在先证者第5号外显子发现KCNQ2基因杂合突变G812T,导致KCNQ2蛋白孔区一个甘氨酸被缬氨酸替代(G271 V),这个位置的甘氨酸在KCNQ家族进化上高度保守。此突变与以前发现的良性家族性新生儿惊厥(benign familial neonatal convulsion,BFNC)家系KCNQ3突变(G310V)是同一位置相同的氨基酸改变。家系中其他患儿均检出与先证者相同的突变,而家系内参加本研究的健康人和家系外75名健康对照未出现这种突变。结论KCNQ2基因突变可能是部分BFIC的分子发病机制,KCNQ2基因G812T突变是国内外未曾报道过的新突变,进一步开展G812T突变的功能研究有助于理解BFIC及其他原发性癫癎的分子发病机理。
Objective To analyze the relationship between the voltage-gated K + channel gene KCNQ2 and a family of benign familial infantile convulsions (BFIC), and to explore the molecular genetic mechanism of BFIC. Methods A blood sample from 41 pedigrees and 75 healthy controls outside the family was collected from a 4-generation BFIC pedigree in Shaanxi Province of China. The KCNQ2 gene mutation was analyzed by PCR amplification and DNA direct sequencing. Polymerase chain reaction-single strand conformation The genotypes and phenotypes were co-segregated. Results PCR-DNA direct sequencing revealed a heterozygous mutation of KCNQ2 gene G812T in exon 5 of proband, resulting in the substitution of a glycine (G271V) in the KCNQ2 domain by glycine at the evolutionarily high level of the KCNQ family Conservative. This mutation is the same amino acid change at the same position as previously found in the familial familial neonatal convulsion (BFNC) family KCNQ3 mutation (G310V). The other mutations in the pedigrees detected the same mutations as the probands, and no mutations were observed in healthy subjects in the pedigree and in 75 healthy controls outside the pedigree. Conclusions KCNQ2 gene mutation may be the molecular pathogenesis of some BFICs. The G812T mutation of KCNQ2 gene is a new mutation not reported in China and abroad. It is helpful to understand the molecular pathogenesis of BFIC and other primary epilepsy by further studying the function of G812T mutation .