Quick Search:

uzh logo
Browse by:

Zurich Open Repository and Archive

Maintenance: Tuesday, July the 26th 2016, 07:00-10:00

ZORA's new graphical user interface will be relaunched (For further infos watch out slideshow ZORA: Neues Look & Feel). There will be short interrupts on ZORA Service between 07:00am and 10:00 am. Please be patient.

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-43376

Heinzen, E L; Radtke, R A; Urban, T J; Cavalleri, G L; Depondt, C; Need, A C; Walley, N M; Nicoletti, P; Ge, D; Catarino, C B; Duncan, J S; Kasperaviciūte, D; Tate, S K; Caboclo, L O; Sander, J W; Clayton, L; Linney, K N; Shianna, K V; Gumbs, C E; Smith, J; Cronin, K D; Maia, J M; Doherty, C P; Pandolfo, M; Leppert, D; Middleton, L T; Gibson, R A; Johnson, M R; Matthews, P M; Hosford, D; Kälviäinen, R; Eriksson, K; Kantanen, A M; Dorn, T; Hansen, J; Krämer, G; Steinhoff, B J; Wieser, H G; Zumsteg, D; Ortega, M; Wood, N W; Huxley-Jones, J; Mikati, M; Gallentine, W B; Husain, A M; Buckley, P G; Stallings, R L; Podgoreanu, M V; Delanty, N; Sisodiya, S M; Goldstein, D B (2010). Rare deletions at 16p13.11 predispose to a diverse spectrum of sporadic epilepsy syndromes. American Journal of Human Genetics, 86(5):707-718.

[img] PDF - Registered users only
View at publisher


Deletions at 16p13.11 are associated with schizophrenia, mental retardation, and most recently idiopathic generalized epilepsy. To evaluate the role of 16p13.11 deletions, as well as other structural variation, in epilepsy disorders, we used genome-wide screens to identify copy number variation in 3812 patients with a diverse spectrum of epilepsy syndromes and in 1299 neurologically-normal controls. Large deletions (> 100 kb) at 16p13.11 were observed in 23 patients, whereas no control had a deletion greater than 16 kb. Patients, even those with identically sized 16p13.11 deletions, presented with highly variable epilepsy phenotypes. For a subset of patients with a 16p13.11 deletion, we show a consistent reduction of expression for included genes, suggesting that haploinsufficiency might contribute to pathogenicity. We also investigated another possible mechanism of pathogenicity by using hybridization-based capture and next-generation sequencing of the homologous chromosome for ten 16p13.11-deletion patients to look for unmasked recessive mutations. Follow-up genotyping of suggestive polymorphisms failed to identify any convincing recessive-acting mutations in the homologous interval corresponding to the deletion. The observation that two of the 16p13.11 deletions were larger than 2 Mb in size led us to screen for other large deletions. We found 12 additional genomic regions harboring deletions > 2 Mb in epilepsy patients, and none in controls. Additional evaluation is needed to characterize the role of these exceedingly large, non-locus-specific deletions in epilepsy. Collectively, these data implicate 16p13.11 and possibly other large deletions as risk factors for a wide range of epilepsy disorders, and they appear to point toward haploinsufficiency as a contributor to the pathogenicity of deletions.


138 citations in Web of Science®
143 citations in Scopus®
Google Scholar™



2 downloads since deposited on 26 Jan 2011
0 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Deposited On:26 Jan 2011 17:54
Last Modified:05 Apr 2016 14:39
Publisher:American Society of Human Genetics
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:10.1016/j.ajhg.2010.03.018
PubMed ID:20398883

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page