GABRA1 and STXBP1: Novel genetic causes of Dravet syndrome
GABRA1 and STXBP1: Novel genetic causes of Dravet syndrome
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DOI：
10.1212/wnl.0000000000000291
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发表时间：
2014-04-08
期刊：
影响因子：
9.9
通讯作者：
Mefford, Heather C.
中科院分区：
文献类型：
--
作者：
Carvill, Gemma L.;Weckhuysen, Sarah;Mefford, Heather C.
目的：为了确定Dravet综合征的患者谁不具有SCN1A突变的常规testing.Methods：我们进行了全外显子组测序在13个SCN1A阴性的Dravet综合征患者和有针对性的重测序在67个额外的患者，以确定新的基因为这种disorder.Results：我们检测到致病突变的2个新的基因Dravet综合征，突变GABRA1在4例和STXBP1在3。此外，我们确定了3例以前未检测到的SCN1A突变，这表明SCN1A突变发生在甚至超过目前接受的近似75%的cases.Conclusions：我们表明，GABRA1和STXBP1作出显着贡献后，SCN1A异常已被排除Dravet综合征。我们的研究结果对诊断测试，临床管理和遗传咨询的患者及其家庭这种毁灭性的疾病有重要意义。
Objective:To determine the genes underlying Dravet syndrome in patients who do not have an SCN1A mutation on routine testing.Methods:We performed whole-exome sequencing in 13 SCN1A-negative patients with Dravet syndrome and targeted resequencing in 67 additional patients to identify new genes for this disorder.Results:We detected disease-causing mutations in 2 novel genes for Dravet syndrome, with mutations in GABRA1 in 4 cases and STXBP1 in 3. Furthermore, we identified 3 patients with previously undetected SCN1A mutations, suggesting that SCN1A mutations occur in even more than the currently accepted approximate to 75% of cases.Conclusions:We show that GABRA1 and STXBP1 make a significant contribution to Dravet syndrome after SCN1A abnormalities have been excluded. Our results have important implications for diagnostic testing, clinical management, and genetic counseling of patients with this devastating disorder and their families.