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Maternally derived microduplications at 15q11-q13: implication of imprinted genes in psychotic illness.


ABSTRACT: OBJECTIVE:Rare copy number variants have been implicated in different neurodevelopmental disorders, with the same copy number variants often increasing risk of more than one of these phenotypes. In a discovery sample of 22 schizophrenia patients with an early onset of illness (10-15 years of age), the authors observed in one patient a maternally derived 15q11-q13 duplication overlapping the Prader-Willi/Angelman syndrome critical region. This prompted investigation of the role of 15q11-q13 duplications in psychotic illness. METHOD:The authors scanned 7,582 patients with schizophrenia or schizoaffective disorder and 41,370 comparison subjects without known psychiatric illness for copy number variants at 15q11-q13 and determined the parental origin of duplications using methylation-sensitive Southern hybridization analysis. RESULTS:Duplications were found in four case patients and five comparison subjects. All four case patients had maternally derived duplications (0.05%), while only three of the five comparison duplications were maternally derived (0.007%), resulting in a significant excess of maternally derived duplications in case patients (odds ratio=7.3). This excess is compatible with earlier observations that risk for psychosis in people with Prader-Willi syndrome caused by maternal uniparental disomy is much higher than in those caused by deletion of the paternal chromosome. CONCLUSIONS:These findings suggest that the presence of two maternal copies of a fragment of chromosome 15q11.2-q13.1 that overlaps with the Prader-Willi/Angelman syndrome critical region may be a rare risk factor for schizophrenia and other psychoses. Given that maternal duplications of this region are among the most consistent cytogenetic observations in autism, the findings provide further support for a shared genetic etiology between autism and psychosis.

SUBMITTER: Ingason A 

PROVIDER: S-EPMC3428917 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Maternally derived microduplications at 15q11-q13: implication of imprinted genes in psychotic illness.

Ingason Andrés A   Kirov George G   Giegling Ina I   Hansen Thomas T   Isles Anthony R AR   Jakobsen Klaus D KD   Kristinsson Kari T KT   le Roux Louise L   Gustafsson Omar O   Craddock Nick N   Möller Hans-Jürgen HJ   McQuillin Andrew A   Muglia Pierandrea P   Cichon Sven S   Rietschel Marcella M   Ophoff Roel A RA   Djurovic Srdjan S   Andreassen Ole A OA   Pietiläinen Olli P H OP   Peltonen Leena L   Dempster Emma E   Collier David A DA   St Clair David D   Rasmussen Henrik B HB   Glenthøj Birte Y BY   Kiemeney Lambertus A LA   Franke Barbara B   Tosato Sarah S   Bonetto Chiara C   Saemundsen Evald E   Hreidarsson Stefán J SJ   Nöthen Markus M MM   Gurling Hugh H   O'Donovan Michael C MC   Owen Michael J MJ   Sigurdsson Engilbert E   Petursson Hannes H   Stefansson Hreinn H   Rujescu Dan D   Stefansson Kari K   Werge Thomas T  

The American journal of psychiatry 20110215 4


<h4>Objective</h4>Rare copy number variants have been implicated in different neurodevelopmental disorders, with the same copy number variants often increasing risk of more than one of these phenotypes. In a discovery sample of 22 schizophrenia patients with an early onset of illness (10-15 years of age), the authors observed in one patient a maternally derived 15q11-q13 duplication overlapping the Prader-Willi/Angelman syndrome critical region. This prompted investigation of the role of 15q11-q  ...[more]

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