Article (Scientific journals)
Estimating the effect size of the 15Q11.2 BP1-BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice.
Jonch, Aia Elise; Douard, Elise; Moreau, Clara et al.
2019In Journal of Medical Genetics, 56 (10), p. 701-710
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Keywords :
15q11.2 copy-number variants; congenital heart disease; epilepsy; loss-of-function intolerance; neurodevelopmental disorders
Abstract :
[en] BACKGROUND: 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 '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.
Disciplines :
Genetics & genetic processes
Author, co-author :
Jonch, Aia Elise
Douard, Elise
Moreau, Clara
Van Dijck, Anke
Passeggeri, Marzia
Kooy, Frank
Puechberty, Jacques
Campbell, Carolyn
Sanlaville, Damien
Lefroy, Henrietta
Richetin, Sonia
Pain, Aurelie
Genevieve, David
Kini, Usha
Le Caignec, Cedric
Lespinasse, James
Skytte, Anne-Bine
Isidor, Bertrand
Zweier, Christiane
CABERG, Jean-Hubert ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Unité de laboratoire - neurogénétique
Delrue, Marie-Ange
Moller, Rikke Steensbjerre
Bojesen, Anders
Hjalgrim, Helle
Brasch-Andersen, Charlotte
Lemyre, Emmanuelle
Ousager, Lilian Bomme
Jacquemont, Sebastien
More authors (18 more) Less
Other collaborator :
DEBRAY, François-Guillaume ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Centre de prise en charge des maladies métaboliques
Language :
English
Title :
Estimating the effect size of the 15Q11.2 BP1-BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice.
Publication date :
2019
Journal title :
Journal of Medical Genetics
ISSN :
0022-2593
eISSN :
1468-6244
Publisher :
BMJ Publishing Group, United Kingdom
Volume :
56
Issue :
10
Pages :
701-710
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c) Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Available on ORBi :
since 08 January 2020

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