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.
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.
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Authors: Kai Wang; Mingyao Li; Dexter Hadley; Rui Liu; Joseph Glessner; Struan F A Grant; Hakon Hakonarson; Maja Bucan Journal: Genome Res Date: 2007-10-05 Impact factor: 9.043
Authors: Y H Jiang; D Armstrong; U Albrecht; C M Atkins; J L Noebels; G Eichele; J D Sweatt; A L Beaudet Journal: Neuron Date: 1998-10 Impact factor: 17.173
Authors: Marianne Doornbos; Birgit Sikkema-Raddatz; Claudia A L Ruijvenkamp; Trijnie Dijkhuizen; Emilia K Bijlsma; Antoinet C J Gijsbers; Yvonne Hilhorst-Hofstee; Roel Hordijk; Krijn T Verbruggen; W S Mieke Kerstjens-Frederikse; Ton van Essen; Klaas Kok; Anneke T van Silfhout; Martijn Breuning; Conny M A van Ravenswaaij-Arts Journal: Eur J Med Genet Date: 2009-03-27 Impact factor: 2.708
Authors: Trygve E Bakken; Cinnamon S Bloss; J Cooper Roddey; Alexander H Joyner; Lars M Rimol; Srdjan Djurovic; Ingrid Melle; Kjetil Sundet; Ingrid Agartz; Ole A Andreassen; Anders M Dale; Nicholas J Schork Journal: Arch Gen Psychiatry Date: 2011-08
Authors: Matthew F Pescosolido; Ece D Gamsiz; Shailender Nagpal; Eric M Morrow Journal: J Am Acad Child Adolesc Psychiatry Date: 2013-04 Impact factor: 8.829