A second locus for familial generalized epilepsy with febrile seizures plus maps to chromosome 2q21-q33
A second locus for familial generalized epilepsy with febrile seizures plus maps to chromosome 2q21-q33
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DOI：
10.1086/302593
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发表时间：
1999-10-01
影响因子：
9.8
通讯作者：
LeGuern, E
中科院分区：
文献类型：
--
作者：
Baulac, S;Gourfinkel-An, I;LeGuern, E
我们报告了Berkovic及其同事描述的一个具有类似全身性癫痫伴热性惊厥+（GEFS+）表型的家族的临床和遗传学研究。患者表现出非常多变的表型，包括热性惊厥、>6岁时经常由发热引起的全身性惊厥和部分性惊厥，严重程度不同。连锁分析排除了负责GEFS（+）的电压门控钠（Na+）通道的β 1亚基基因（SCN 1B）和先前与热性惊厥有关的两个位点FEB 1和FEB 2。全基因组搜索，假设在85%的不完全重复率和5%的表型复制率，允许识别染色体2 q21-q33上的一个新位点。标记D2 S2330的最大成对LOD评分为3.00，重组分数为0。单倍型重建定义了一个大的（22厘米）候选间隔两侧的标记D2 S156和D2 S2314。位于该区域的编码不同亚型的Cu亚基电压门控钠通道（SCN 1A、SCN 2A 1、SCN 2A 2和SCN 3A）的四个基因是该疾病基因的强有力候选者。
We report a clinical and genetic study of a family with a phenotype resembling generalized epilepsy with febrile seizures plus (GEFS+), described by Berkovic and colleagues. Patients express a very variable phenotype combining febrile seizures, generalized seizures often precipitated by fever at age >6 years, and partial seizures, with a variable degree of severity. Linkage analysis has excluded both the beta 1 subunit gene (SCN1B) of a voltage-gated sodium (Na+) channel responsible for GEFS(+) and the two loci, FEB1 and FEB2, previously implicated in febrile seizures. A genomewide search, under the assumption of incomplete penetrance at 85% and a phenocopy rate of 5%, permitted identification of a new locus on chromosome 2q21-q33. The maximum pairwise LOD score was 3.00 at recombination fraction 0 for marker D2S2330. Haplotype reconstruction defined a large (22-cM) candidate interval flanked by markers D2S156 and D2S2314. Four genes coding for different isoforms of the cu-subunit voltage-gated sodium channels (SCN1A, SCN2A1, SCN2A2, and SCN3A) located in this region are strong candidates for the disease gene.