Estimating the effect size of the 15Q11.2 BP1-BP2 deletion and its contribution to neurodevelopmental symptoms: Recommendations for practice

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  • Aia Elise Jønch, Odense Universitetshospital, Syddansk Universitet
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  • Elise Douard, Center Hospitalier Universitaire Sainte-Justine Research Center, University of Montreal
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  • Clara Moreau, Center Hospitalier Universitaire Sainte-Justine Research Center, University of Montreal
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  • Anke Van Dijck, University of Antwerp
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  • Marzia Passeggeri, Service of Medical Genetics, CHUV Lausanne
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  • Frank Kooy, University of Antwerp
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  • Jacques Puechberty, univ Montpellier
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  • Carolyn Campbell, Oxford University, Oxford, UK.
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  • Damien Sanlaville, Hospices Civils de Lyon, Claude Bernard University Lyon 1
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  • Henrietta Lefroy, Oxford University, Oxford, UK.
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  • Sonia Richetin, Service of Medical Genetics, CHUV Lausanne
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  • Aurelie Pain, Service of Medical Genetics, CHUV Lausanne
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  • David Geneviève, univ Montpellier, Hopital Saint-Eloi
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  • Usha Kini, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital
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  • Cédric Le Caignec, CHU Nantes
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  • James Lespinasse, Centre Hospitalier de Chambéry
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  • Anne Bine Skytte
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  • Bertrand Isidor, CHU Nantes
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  • Christiane Zweier, Friedrich-Alexander-Universität Erlangen-Nürnberg
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  • Jean Hubert Caberg, University of Liege
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  • Marie Ange Delrue, Center Hospitalier Universitaire Sainte-Justine Research Center, University of Montreal
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  • Rikke Steensbjerre Møller, Danish Epilepsy Centre, Dianalund
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  • Anders Bojesen, Vejle Sygehus, Vejle, Denmark.
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  • Helle Hjalgrim, Danish Epilepsy Centre, Dianalund
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  • Charlotte Brasch-Andersen, Odense Universitetshospital, Syddansk Universitet
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  • Emmanuelle Lemyre, Center Hospitalier Universitaire Sainte-Justine Research Center, University of Montreal
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  • Lilian Bomme Ousager, Odense Universitetshospital, Syddansk Universitet
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  • Sébastien Jacquemont, Center Hospitalier Universitaire Sainte-Justine Research Center, University of Montreal
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  • 15q11.2 Working Group

The 15q11.2 deletion is frequently identified in the neurodevelopmental clinic. Case-control studies have associated the 15q11.2 deletion with neurodevelopmental disorders, and clinical case series have attempted to delineate a microdeletion syndrome with considerable phenotypic variability. The literature on this deletion is extensive and confusing, which is a challenge for genetic counselling. The aim of this study was to estimate the effect size of the 15q11.2 deletion and quantify its contribution to neurodevelopmental disorders. Methods We performed meta-analyses on new and previously published case-control studies and used statistical models trained in unselected populations with cognitive assessments. We used new (n=241) and previously published (n=150) data from a clinically referred group of deletion carriers. 15q11.2 duplications (new n=179 and previously published n=35) were used as a neutral control variant. Results The deletion decreases IQ by 4.3 points. The estimated ORs and respective frequencies in deletion carriers for intellectual disabilities, schizophrenia and epilepsy are 1.7 (3.4%), 1.5 (2%) and 3.1 (2.1%), respectively. There is no increased risk for heart malformations and autism. In the clinically referred group, the frequency and nature of symptoms in deletions are not different from those observed in carriers of the 15q11.2 duplication suggesting that most of the reported symptoms are due to ascertainment bias. Conclusions We recommend that the deletion should be classified as a € pathogenic of mild effect size'. Since it explains only a small proportion of the phenotypic variance in carriers, it is not worth discussing in the developmental clinic or in a prenatal setting.

Original languageEnglish
JournalJournal of Medical Genetics
Volume56
Issue10
Pages (from-to)701-710
Number of pages10
ISSN0022-2593
DOIs
Publication statusPublished - Oct 2019

    Research areas

  • 15q11.2 copy-number variants, congenital heart disease, epilepsy, loss-of-function intolerance, neurodevelopmental disorders

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