Exome-wide analysis of mutational burden in patients with typical and atypical Rolandic epilepsy

被引：19

作者：

Bobbili, Dheeraj R. ^{[1
]}

Lal, Dennis ^{[2
,3
,4
,5
,6
]}

May, Patrick ^{[1
]}

Reinthaler, Eva M. ^{[7
]}

Jabbari, Kamel ^{[8
]}

Thiele, Holger ^{[2
]}

Nothnagel, Michael ^{[2
]}

Jurkowski, Wiktor ^{[1
,9
]}

Feucht, Martha ^{[10
,13
]}

Nuernberg, Peter ^{[2
]}

Lerche, Holger ^{[11
]}

Zimprich, Fritz ^{[7
]}

Krause, Roland ^{[1
]}

Neubauer, Bernd A. ^{[12
]}

Reinthaler, Eva M. ^{[7
]}

Zimprich, Fritz ^{[7
]}

Feucht, Martha ^{[10
,13
]}

Steinboeck, Hannelore ^{[14
]}

Neophytou, Birgit ^{[15
]}

Geldner, Julia ^{[16
]}

Gruber-Sedlmayr, Ursula ^{[17
]}

Haberlandt, Edda ^{[18
]}

Ronen, Gabriel M. ^{[19
]}

Altmueller, Janine ^{[2
]}

Lal, Dennis ^{[2
,3
,4
,5
,6
]}

Nrnberg, Peter ^{[2
]}

Sander, Thomas ^{[2
]}

Thiele, Holger ^{[2
]}

Krause, Roland ^{[1
]}

May, Patrick ^{[1
]}

Balling, Rudi ^{[1
]}

Lerche, Holger ^{[11
]}

Neubauer, Bernd A. ^{[12
]}

机构：

[1] Univ Luxembourg, Luxembourg Ctr Syst Biomed, Esch Sur Alzette, Luxembourg

[2] Univ Cologne, Cologne Ctr Genom, Cologne, Germany

[3] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA

[4] Harvard Med Sch, Boston, MA USA

[5] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA

[6] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA

[7] Med Univ Vienna, Dept Neurol, Vienna, Austria

[8] Univ Cologne, Inst Genet, Cologne Bioctr, Cologne, Germany

[9] Genome Anal Ctr, Norwich, Norfolk, England

[10] Med Univ Vienna, Dept Pediat, Vienna, Austria

[11] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurol & Epileptol, Tubingen, Germany

[12] Univ Giessen, Fac Med, Dept Neuropediat, Giessen, Germany

[13] Med Univ Vienna, Dept Pediat & Adolescent Med, A-1090 Vienna, Austria

[14] St Anna Childrens Hosp, Private Practice Pediat, A-1150 Vienna, Austria

[15] Dept Neuropediat, A-1090 Vienna, Austria

[16] Hosp SMZ Sud Kaiser Franz Josef, Dept Pediat, A-1100 Vienna, Austria

[17] Med Univ Graz, Dept Pediat, A-8036 Graz, Austria

[18] Med Univ Innsbruck, Dept Pediat, A-6020 Innsbruck, Austria

[19] McMaster Univ, Dept Pediat, Hamilton, ON L8N 3Z5, Canada

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2018年 / 26卷 / 02期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

FRAMEWORK; GENES; VARIANTS; AUTISM;

D O I：

10.1038/s41431-017-0034-x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Rolandic epilepsy (RE) is the most common focal epilepsy in childhood. To date no hypothesis-free exome-wide mutational screen has been conducted for RE and atypical RE (ARE). Here we report on whole-exome sequencing of 194 unrelated patients with RE/ARE and 567 ethnically matched population controls. We identified an exome-wide significantly enriched burden for deleterious and loss-of-function variants only for the established RE/ARE gene GRIN2A. The statistical significance of the enrichment disappeared after removing ARE patients. For several disease-related gene-sets, an odds ratio >1 was detected for loss-of-function variants.

引用

页码：258 / 264

页数：7

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