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Genetics of epilepsy: The testimony of twins in the molecular era.

Authors :
Vadlamudi L
Milne RL
Lawrence K
Heron SE
Eckhaus J
Keay D
Connellan M
Torn-Broers Y
Howell RA
Mulley JC
Scheffer IE
Dibbens LM
Hopper JL
Berkovic SF
Source :
Neurology [Neurology] 2014 Sep 16; Vol. 83 (12), pp. 1042-8. Date of Electronic Publication: 2014 Aug 08.
Publication Year :
2014

Abstract

Objective: Analysis of twins with epilepsy to explore the genetic architecture of specific epilepsies, to evaluate the applicability of the 2010 International League Against Epilepsy (ILAE) organization of epilepsy syndromes, and to integrate molecular genetics with phenotypic analyses.<br />Methods: A total of 558 twin pairs suspected to have epilepsy were ascertained from twin registries (69%) or referral (31%). Casewise concordance estimates were calculated for epilepsy syndromes. Epilepsies were then grouped according to the 2010 ILAE organizational scheme. Molecular genetic information was utilized where applicable.<br />Results: Of 558 twin pairs, 418 had confirmed seizures. A total of 534 twin individuals were affected. There were higher twin concordance estimates for monozygotic (MZ) than for dizygotic (DZ) twins for idiopathic generalized epilepsies (MZ = 0.77; DZ = 0.35), genetic epilepsy with febrile seizures plus (MZ = 0.85; DZ = 0.25), and focal epilepsies (MZ = 0.40; DZ = 0.03). Utilizing the 2010 ILAE scheme, the twin data clearly demonstrated genetic influences in the syndromes designated as genetic. Of the 384 tested twin individuals, 10.9% had mutations of large effect in known epilepsy genes or carried validated susceptibility alleles.<br />Conclusions: Twin studies confirm clear genetic influences for specific epilepsies. Analysis of the twin sample using the 2010 ILAE scheme strongly supported the validity of grouping the "genetic" syndromes together and shows this organizational scheme to be a more flexible and biologically meaningful system than previous classifications. Successful selected molecular testing applied to this cohort is the prelude to future large-scale next-generation sequencing of epilepsy research cohorts. Insights into genetic architecture provided by twin studies provide essential data for optimizing such approaches.<br /> (© 2014 American Academy of Neurology.)

Details

Language :
English
ISSN :
1526-632X
Volume :
83
Issue :
12
Database :
MEDLINE
Journal :
Neurology
Publication Type :
Academic Journal
Accession number :
25107880
Full Text :
https://doi.org/10.1212/WNL.0000000000000790