作者
Gemma L Carvill, Sarah Weckhuysen, Jacinta M McMahon, Corinna Hartmann, Rikke S Møller, Helle Hjalgrim, Joseph Cook, Eileen Geraghty, Brian J O’Roak, Steve Petrou, Alison Clarke, Deepak Gill, Lynette G Sadleir, Hiltrud Muhle, Sarah Von Spiczak, Marina Nikanorova, Bree L Hodgson, Elena V Gazina, Arvid Suls, Jay Shendure, Leanne M Dibbens, Peter De Jonghe, Ingo Helbig, Samuel F Berkovic, Ingrid E Scheffer, Heather C Mefford
发表日期
2014/4/8
期刊
Neurology
卷号
82
期号
14
页码范围
1245-1253
出版商
Lippincott Williams & Wilkins
简介
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 ∼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 …
学术搜索中的文章
GL Carvill, S Weckhuysen, JM McMahon, C Hartmann… - Neurology, 2014