RT Journal Article
SR Electronic
T1 Estimating the effect size of the 15Q11.2 BP1–BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 701
OP 710
DO 10.1136/jmedgenet-2018-105879
VO 56
IS 10
A1 Aia Elise Jønch
A1 Elise Douard
A1 Clara Moreau
A1 Anke Van Dijck
A1 Marzia Passeggeri
A1 Frank Kooy
A1 Jacques Puechberty
A1 Carolyn Campbell
A1 Damien Sanlaville
A1 Henrietta Lefroy
A1 Sonia Richetin
A1 Aurelie Pain
A1 David Geneviève
A1 Usha Kini
A1 Cédric Le Caignec
A1 James Lespinasse
A1 Anne-Bine Skytte
A1 Bertrand Isidor
A1 Christiane Zweier
A1 Jean-Hubert Caberg
A1 Marie-Ange Delrue
A1 Rikke Steensbjerre Møller
A1 Anders Bojesen
A1 Helle Hjalgrim
A1 Charlotte Brasch-Andersen
A1 Emmanuelle Lemyre
A1 Lilian Bomme Ousager
A1 Sébastien Jacquemont
A1 ,
YR 2019
UL http://jmg.bmj.com/content/56/10/701.abstract
AB 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.