A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders. Issue 10 (10th October 2012)

• Record Type: Journal Article
• Authors: Zufferey, Flore; Sherr, Elliott H; Beckmann, Noam D; Hanson, Ellen; Maillard, Anne M; Hippolyte, Loyse; Macé, Aurélien; Ferrari, Carina; Kutalik, Zoltán; Andrieux, Joris; Aylward, Elizabeth; Barker, Mandy; Bernier, Raphael; Bouquillon, Sonia; Conus, Philippe; Delobel, Bruno; Faucett, W Andrew; Goin-Kochel, Robin P; Grant, Ellen; Harewood, Louise; Hunter, Jill V; Lebon, Sébastien; Ledbetter, David H; Martin, Christa Lese; Männik, Katrin; Martinet, Danielle; Mukherjee, Pratik; Ramocki, Melissa B; Spence, Sarah J; Steinman, Kyle J; Tjernagel, Jennifer; Spiro, John E; Reymond, Alexandre; Beckmann, Jacques S; Chung, Wendy K; Jacquemont, Sébastien;
• Other Names: Addor Marie Claude author non-byline.; Arveiler Benoit author non-byline.; Belfiore Marco author non-byline.; Bena Frédérique author non-byline.; Bernardini Laura author non-byline.; Blanchet Patricia author non-byline.; Bonneau Dominique author non-byline.; Boute Odile author non-byline.; Callier Patrick author non-byline.; Campion Dominique author non-byline.; Chiesa Jean author non-byline.; Cordier Marie Pierre author non-byline.; Cuisset Jean Marie author non-byline.; David Albert author non-byline.; de Leeuw Nicole author non-byline.; de Vries Bert author non-byline.; Didelot Gérard author non-byline.; Doco-Fenzy Martine author non-byline.; Bedu Bénédicte Duban author non-byline.; Dubourg Christèle author non-byline.; Dupuis-Girod Sophie author non-byline.; Fagerberg Christina R. author non-byline.; Faivre Laurence author non-byline.; Fellmann Florence author non-byline.; Fernandez Bridget A. author non-byline.; Fisher Richard author non-byline.; Flori Elisabeth author non-byline.; Goldenberg Alice author non-byline.; Heron Delphine author non-byline.; Holder Muriel author non-byline.; Hoyer Juliane author non-byline.; Isidor Bertrand author non-byline.; Jaillard Sylvie author non-byline.; Jonveaux Philippe author non-byline.; Joriot Sylvie author non-byline.; Journel Hubert author non-byline.; Kooy Frank author non-byline.; le Caignec Cédric author non-byline.; Leheup Bruno author non-byline.; Lemaitre Marie-Pierre author non-byline.; Lewis Suzanne author non-byline.; Malan Valérie author non-byline.; Mathieu-Dramard Michèle author non-byline.; Metspalu Andres author non-byline.; Morice-Picard Fanny author non-byline.; Mucciolo Mafalda author non-byline.; Oiglane-Shlik Eve author non-byline.; Ounap Katrin author non-byline.; Pasquier Laurent author non-byline.; Petit Florence author non-byline.; Philippe Anne author non-byline.; Plessis Ghislaine author non-byline.; Prieur Fabienne author non-byline.; Puechberty Jacques author non-byline.; Rajcan-Separovic Evica author non-byline.; Rauch Anita author non-byline.; Renieri Alessandra author non-byline.; Rieubland Claudine author non-byline.; Rooryck Caroline author non-byline.; Rötzer Katharina Magdalena author non-byline.; Ruiter Mariken author non-byline.; Sanlaville Damien author non-byline.; Selmoni Stéphanie author non-byline.; Shen Yiping author non-byline.; Siffredi Vanessa author non-byline.; Thonney Jacques author non-byline.; Vallée Louis author non-byline.; van Binsbergen Ellen author non-byline.; Van der Aa Nathalie author non-byline.; van Haelst Mieke M. author non-byline.; Vigneron Jacqueline author non-byline.; Vincent-Delorme Catherine author non-byline.; Vittoria Disciglio author non-byline.; Vulto-van Silfhout Anneke T author non-byline.; Witwicki Robert M author non-byline.; Zwolinski Simon A. author non-byline.; Bowe Alexandra author non-byline.; Beaudet Arthur L author non-byline.; Brewton Christie M author non-byline.; Chu Zili author non-byline.; Dempsey Allison G author non-byline.; Evans Yolanda L author non-byline.; Garza Silvia author non-byline.; Kanne Stephen M author non-byline.; Laakman Anna L author non-byline.; Lasala Morgan W author non-byline.; Llorens Ashlie V author non-byline.; Marzano Gabriela author non-byline.; Moss Timothy J author non-byline.; Nowell Kerri P author non-byline.; Proud Monica B author non-byline.; Chen Qixuan author non-byline.; Vaughan Roger author non-byline.; Berman Jeffrey author non-byline.; Blaskey Lisa author non-byline.; Hines Katherine author non-byline.; Kessler Sudha author non-byline.; Khan Sarah Y author non-byline.; Qasmieh Saba author non-byline.; Bibb Audrey Lynn author non-byline.; Paal Andrea M author non-byline.; Page Patricia Z author non-byline.; Smith-Packard Bethanny author non-byline.; Buckner Randy author non-byline.; Burko Jordan author non-byline.; Cavanagh Alyss Lian author non-byline.; Cerban Bettina author non-byline.; Snow Anne V author non-byline.; Snyder LeeAnne Green author non-byline.; Keehn Rebecca McNally author non-byline.; Miller David T author non-byline.; Miller Fiona K author non-byline.; Olson Jennifer Endre author non-byline.; Triantafallou Christina author non-byline.; Visyak Nicole author non-byline.; Atwell Constance author non-byline.; Benedetti Marta author non-byline.; Fischbach Gerald D author non-byline.; Greenup Marion author non-byline.; Packer Alan author non-byline.; Bukshpun Polina author non-byline.; Cheong Maxwell author non-byline.; Dale Corby author non-byline.; Gobuty Sarah E author non-byline.; Hinkley Leighton author non-byline.; Jeremy Rita J author non-byline.; Lee Hana author non-byline.; Luks Tracy L author non-byline.; Marco Elysa J author non-byline.; Martin Alastair J author non-byline.; McGovern Kathleen E author non-byline.; Nagarajan Srikantan S author non-byline.; Owen Julia author non-byline.; Paul Brianna M author non-byline.; Pojman Nicholas J author non-byline.; Sinha Tuhin author non-byline.; Swarnakar Vivek author non-byline.; Wakahiro Mari author non-byline.; Alupay Hanalore author non-byline.; Aaronson Benjamin author non-byline.; Ackerman Sean author non-byline.; Ankenman Katy author non-byline.; Elgin Jenna author non-byline.; Gerdts Jennifer author non-byline.; Johnson Kelly author non-byline.; Reilly Beau author non-byline.; Shaw Dennis author non-byline.; Stevens Arianne author non-byline.; Ward Tracey author non-byline.; Wenegrat Julia author non-byline.; Roberts Timothy PL author non-byline.;
• Is Part Of: Journal of medical genetics. Volume 49:Issue 10(2012)
• Page Start: 660
• Page End: 668
• Publication Date: 2012-10-10
• Subjects: Clinical genetics -- Obesity -- Psychiatry -- Complex traits; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2012-101203
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Background: The recurrent ∼600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders. Objective: To define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion. Methods: We collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers and 68 intrafamilial non-carrier controls. Results: When compared to intrafamilial controls, full scale intelligence quotient (FSIQ) is two standard deviations lower in carriers, and there is no difference between carriers referred for neurodevelopmental disorders and carriers identified through cascade family testing. Verbal IQ (mean 74) is lower than non-verbal IQ (mean 83) and a majority of carriers require speech therapy. Over 80% of individuals exhibit psychiatric disorders including ASD, which is present in 15% of the paediatric carriers. Increase in head circumference (HC) during infancy is similar to the HC and brain growth patterns observed in idiopathic ASD. Obesity, a major comorbidity present in 50% of the carriers by the age of 7 years, does not correlate with FSIQ or any behavioural trait. Seizures are present in 24% of carriers and occur independently of other symptoms. Malformations are infrequently found, confirming only a few of the previously reported associations. Conclusions: The 16p11.2 deletion impacts in a quantitative and independent manner FSIQ, behaviour and body mass index, possibly through direct influences on neural circuitry. Although non-specific, these features are clinically significant and reproducible. Lastly, this study demonstrates the necessity of studying large patient cohorts ascertained through multiple methods to characterise the clinical consequences of rare variants involved in common diseases.