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Autism Spectrum Disorder, Developmental and Psychiatric Features in 16p11.2 Duplication

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Abstract

The 16p11.2 duplication (BP4–BP5) is associated with Autism Spectrum Disorder (ASD), although significant heterogeneity exists. Quantitative ASD, behavioral and neuropsychological measures and DSM-IV diagnoses in child and adult carriers were compared with familial non-carrier controls, and to published results from deletion carriers. The 16p11.2 duplication phenotype ranges widely from asymptomatic presentation to significant disability. The most common diagnoses were intellectual disability, motor delays and Attention Deficit Hyperactivity Disorder in children, and anxiety in adults. ASD occurred in nearly 20 % of child cases, but a majority of carriers did not show the unique social features of ASD. The 16p11.2 duplication phenotype is characterized by wider variability than the reciprocal deletion, likely reflecting contributions from additional risk factors.

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Acknowledgments

This study was funded by a grant from the Simons Foundation (SFARI award #198677 to EH, RB, RGK, ES, TR, CLM, DHL and WKC).

We are grateful to all of the families at the participating Simons Variation in Individuals Project (Simons VIP) sites, as well as the Simons VIP working group (Simons VIP consortium, Neuron, 73(6):1063–1067, 2012). We are also grateful for the guidance and support from Cathy Lord and Helen Tager-Flusberg on the development of this project.

We appreciate obtaining access to phenotypic data on SFARI Base.

Approved researchers can obtain the Simons VIP population dataset described in this study by applying at https://base.sfari.org.

The Simons VIP Consortium includes: Hanalore Alupay, Benjamin Aaronson, Sean Ackerman, Katy Ankenman, Ayesha Anwar, Constance Atwell, Alexandra Bowe, Arthur L Beaudet, Marta Benedetti, Jessica Berg, Jeffrey Berman, Leandra N Berry, Audrey L Bibb, Lisa Blaskey, Jonathan Brennan, Christie M Brewton, Randy Buckner, Polina Bukshpun, Jordan Burko, Phil Cali, Bettina Cerban, Yishin Chang, Maxwell Cheong, Vivian Chow, Zili Chu, Darina Chudnovskaya, Lauren Cornew, Corby Dale, John Dell, Allison G Dempsey, Trent Deschamps, Rachel Earl, James Edgar, Jenna Elgin, Jennifer Endre Olson, Yolanda L Evans, Anne Findlay, Gerald D Fischbach, Charlie Fisk, Brieana Fregeau, Bill Gaetz, Leah Gaetz, Silvia Garza, Jennifer Gerdts, Orit Glenn, Sarah E Gobuty, Rachel Golembski, Marion Greenup, Kory Heiken, Katherine Hines, Leighton Hinkley, Frank I Jackson, Julian Jenkins III, Rita J Jeremy, Kelly Johnson, Stephen M Kanne, Sudha Kessler, Scrah Y Khan, Matthew Ku, Emily Kuschner, Anna L Laakman, Peter Lam, Morgan W Lasala, Hana Lee, Kevin LeGuerre, Susan Levy, Alyss Lian Cavanagh, Ashlie V Llorens, Katherine Loftus Campe, Tracy L Luks, Elysa J Marco, Stephen Martin, Alastair J Martin, Gabriela Marzano, Christina Masson, Kathleen E McGovern, Rebecca McNally Keehn, David T Miller, Fiona K Miller, Timothy J Moss, Rebecca Murray, Srikantan S Nagarajan, Kerri P Nowell, Julia Owen, Andrea M Paal, Alan Packer, Patricia Z Page, Brianna M Paul, Alana Peters, Danica Peterson, Annapurna Poduri, Nicholas J Pojman, Ken Porche, Monica B Proud, Saba Qasmieh, Melissa B Ramocki, Beau Reilly, Timothy PL Roberts, Dennis Shaw, Tuhin Sinha, Bethanny Smith-Packard, Anne Snow Gallagher, Vivek Swarnakar, Tony Thieu, Christina Triantafallou, Roger Vaughan, Nicole Visyak, Mari Wakahiro, Arianne Wallace, Tracey Ward, Julia Wenegrat, and Anne Wolken.

Author Contributions

Authors LGS, DA and QC contributed to the design, and analysis and interpretation of the data. LGS, RB, RPGK, EH, ASW, JG, SK, LB, EK, TR, RS and CLM contributed to the design, and acquisition and interpretation of the data. DHL, JES, WKC, LGS and EH contributed to the conception and design, and interpretation of the data. All authors drafted or revised and approved the manuscript.

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Green Snyder, L., D’Angelo, D., Chen, Q. et al. Autism Spectrum Disorder, Developmental and Psychiatric Features in 16p11.2 Duplication. J Autism Dev Disord 46, 2734–2748 (2016). https://doi.org/10.1007/s10803-016-2807-4

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