Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy

被引：302

作者：

Heron, Sarah E. ^{[2
,3
]}

Smith, Katherine R. ^{[4
,5
]}

Bahlo, Melanie ^{[4
,6
]}

Nobili, Lino ^{[7
]}

Kahana, Esther ^{[8
]}

Licchetta, Laura ^{[1
]}

Oliver, Karen L. ^{[1
]}

Mazarib, Aziz ^{[10
]}

Afawi, Zaid ^{[9
]}

Korczyn, Amos ^{[11
]}

Plazzi, Giuseppe ^{[12
]}

Petrou, Steven ^{[13
,14
,15
]}

Berkovic, Samuel F. ^{[1
]}

Scheffer, Ingrid E. ^{[1
,13
,16
]}

Dibbens, Leanne M. ^{[2
,3
]}

机构：

[1] Univ Melbourne, Dept Med, Epilepsy Res Ctr, Melbourne, Vic, Australia

[2] Univ S Australia, Sch Pharm & Med Sci, Epilepsy Res Program, Adelaide, SA 5001, Australia

[3] Univ S Australia, Sansom Inst Hlth Res, Adelaide, SA 5001, Australia

[4] Walter & Eliza Hall Inst Med Res, Bioinformat Div, Melbourne, Vic 3050, Australia

[5] Univ Melbourne, Dept Med Biol, Melbourne, Vic, Australia

[6] Univ Melbourne, Dept Math & Stat, Melbourne, Vic, Australia

[7] Osped Niguarda Ca Granda, Sleep Med Ctr, Epilepsy Surg Ctr, Milan, Italy

[8] Ben Gurion Univ Negev, Sch Hlth Sci, Barzilai Med Ctr, Dept Neurol, IL-84105 Beer Sheva, Israel

[9] Tel Aviv Univ, Sackler Fac Med, Ramat Aviv, Israel

[10] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel

[11] Tel Aviv Univ, Sch Med, Sieratzki Chair Neurol, Ramat Aviv, Israel

[12] Univ Bologna, Dept Neurol Sci, Bologna, Italy

[13] Florey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia

[14] Univ Melbourne, Dept Anat & Neurosci, Melbourne, Vic, Australia

[15] Univ Melbourne, Ctr Neural Engn, Melbourne, Vic, Australia

[16] Univ Melbourne, Royal Childrens Hosp, Dept Paediat, Melbourne, Vic, Australia

来源：

NATURE GENETICS | 2012年 / 44卷 / 11期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

D O I：

10.1038/ng.2440

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We performed genomic mapping of a family with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and intellectual and psychiatric problems, identifying a disease-associated region on chromosome 9q34.3. Whole-exome sequencing identified a mutation in KCNT1, encoding a sodium-gated potassium channel subunit. KCNT1 mutations were identified in two additional families and a sporadic case with severe ADNFLE and psychiatric features. These findings implicate the sodium-gated potassium channel complex in ADNFLE and, more broadly, in the pathogenesis of focal epilepsies.

引用

页码：1188 / 1190

页数：3

共 14 条

[1] Increased sensitivity of the neuronal nicotinic receptor α2 subunit causes familial epilepsy with nocturnal wandering and ictal fear [J].