Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/92758
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dc.contributor.authorVadlamudi, L.en
dc.contributor.authorMilne, R.en
dc.contributor.authorLawrence, K.en
dc.contributor.authorHeron, S.en
dc.contributor.authorEckhaus, J.en
dc.contributor.authorKeay, D.en
dc.contributor.authorConnellan, M.en
dc.contributor.authorTorn-Broers, Y.en
dc.contributor.authorHowell, R.en
dc.contributor.authorMulley, J.en
dc.contributor.authorScheffer, I.en
dc.contributor.authorDibbens, L.en
dc.contributor.authorHopper, J.en
dc.contributor.authorBerkovic, S.en
dc.date.issued2014en
dc.identifier.citationNeurology, 2014; 83(12):1042-1048en
dc.identifier.issn0028-3878en
dc.identifier.issn1526-632Xen
dc.identifier.urihttp://hdl.handle.net/2440/92758-
dc.description.abstractOBJECTIVE: 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. 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. 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. 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.en
dc.description.statementofresponsibilityLata Vadlamudi, Roger L. Milne, Kate Lawrence, Sarah E. Heron, Jazmin Eckhaus, Deborah Keay, Mary Connellan, Yvonne Torn-Broers, R. Anne Howell, John C. Mulley, Ingrid E. Scheffer, Leanne M. Dibbens, John L. Hopper and Samuel F. Berkovicen
dc.language.isoenen
dc.publisherAmerican Academy of Neurologyen
dc.rights© 2014 American Academy of Neurologyen
dc.subjectEpilepsies, Partial; Epilepsy, Generalized; Cohort Studies; Twins, Dizygotic; Twins, Monozygotic; Seizures, Febrile; Genetic Predisposition to Diseaseen
dc.titleGenetics of epilepsy: the testimony of twins in the molecular eraen
dc.typeJournal articleen
dc.identifier.doi10.1212/WNL.0000000000000790en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/628911en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/400121en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/628952en
pubs.publication-statusPublisheden
dc.identifier.orcidHeron, S. [0000-0001-8759-6748]en
Appears in Collections:Paediatrics publications

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