中文摘要：

目的 筛查全面性癫（痫）伴热性惊厥附加症（GEFS＋）家系的SCN1A基因突变类型,探讨GEFS＋基因型与临床表型的相关性.方法 收集17个GEFS＋家系先证者及其家系成员临床资料及外周血DNA,分析家系受累患者的临床表型,并应用PCR产物直接测序技术进行SCN1A基因突变分析.结果 17个家系中发现2个GEFS＋家系（11.76％）存在新SCN1A基因点突变（C142T、S573R）,分别位于第3外显子和第11外显子区,呈杂合子错义突变,以上2个突变位点均属于高度保守区域,国内外尚未见报道.携带C142T突变的家系1先证者及其他家系受累成员临床表型为热性惊厥（FS）或热性惊厥附加症（FS＋）,表现为全面性强直阵挛发作,该家系的突变外显率为75.0％（3/4例）.携带S573R家系2的先证者临床表型为FS＋伴局限性发作,该家系的突变外显率为66.7％（2/3例）.结论 GEFS＋家系中新发现2个SCN1A错义点突变（C142T、S573R）,呈常染色体显性遗传并伴有外显率不全.C142T、S573R突变分别位于钠离子通道α亚单位蛋白结构域D1的S6跨膜片段内和蛋白结构域D4的S5-S6连接环.2个家系携带不同的基因突变位点,其受累成员的主要临床表型也不同.因此,SCN1A基因也是我国GEFS＋家系的致病基因之一,SCN1A基因型与GEFS＋家系的临床表型相关.

英文摘要：

Obgective To investigate the gene mutations of SCN1A in the families with generalized epilepsy with febrile seizures plus （GEFS ＋） and analyze the genotype-phenotype correlations in GEFS ＋ families.Methods Genomic DNA was extracted from peripheral blood lymphocytes of the probands and other available members in the GEFS ＋ families.The phenotypes of the affected members were analyzed.The coding regions and flanking intronic regions of the SCN1A gene were screened for mutations using PCR and direct DNA sequencing.Results Two in 17 families （11.76%） were found with novel SCN1A mutations （C142T,S573 R）,presenting heterozygote missense mutations in exon 3 and exon 11 located in highly conserved region.The above 2 mutations had not been reported.The proband and other affected members in pedigree 1 all carried the mutation（C142T）.Their clinical phenotype included febrile seizures（FS） and FS plus（FS ＋） with generalized tonic-clonic seizures and the penetrance rate was about 75.0% （3/4 cases）.The phenotype of the proband in pedigree 2 harbored S573R were FS ＋ with partial seizures and the penetrance rate was about 66.7% （2/3 cases）.Conclusions Two novel missense mutations were identified in the GEFS ＋ families,which were consistent with autosomal dominant inheritance with incomplete penetrance.C142T located in the S6 transmembrane regions at domain D1 and S573R located between S5-S6 segment at domain D4 in the voltage-gated sodium channel.Two families harbored different genetic mutations,in which the affected members had different clinical phenotypes.SCN1A is one of the pathogenic gene in Chinese GEFS ＋ patients and the genotypes of GEFS ＋ family is associated with the clinical phenotypes.