Zufferey, F, Sherr, EH, Beckmann, ND, Hanson, E, Maillard, AM, Hippolyte, L, Macé, A, Ferrari, C, Kutalik, Z, Andrieux, J, Aylward, E, Barker, M, Bernier, R, Bouquillon, S, Conus, P, Delobel, B, Faucett, WA, Goin-Kochel, RP, Grant, E, Harewood, L, Hunter, JV, Lebon, S, Ledbetter, DH, Martin, CL, Männik, K, Martinet, D, Mukherjee, P, Ramocki, MB, Spence, SJ, Steinman, KJ, Tjernage, J, Spiro, JE, Reymond, A, Beckmann, JS, Chung, WK, Jacquemont, S, Addor, MC, Arveiler, B, Belfiore, M, Bena, F, Bernardini, L, Blanchet, P, Bonneau, D, Boute, O, Callier, P, Campion, D, Chiesa, J, Cordier, MP, Cuisset, JM, David, A, De Leeuw, N, De Vries, B, Didelot, G, Doco-Fenzy, M, Bedu, BD, Dubourg, C, Dupuis-Girod, S, Fagerberg, CR, Faivre, L, Fellmann, F, Fernandez, BA, Fisher, R, Flori, E, Goldenberg, A, Heron, D, Holder, M, Hoyer, J, Isidor, B, Jaillard, S, Jonveaux, P, Joriot, S, Journel, H, Kooy, F, le Caignec, C, Leheup, B, Lemaitre, MP, Lewis, S, Malan, V, Mathieu-Dramard, M, Metspalu, A, Morice-Picard, F, Mucciolo, M, Oiglane-Shlik, E, Ounap, K, Pasquier, L, Petit, F, Philippe, A, Plessis, G, Prieur, F, Puechberty, J, Rajcan-Separovic, E, Rauch, A, Renieri, A, Rieubland, C, Rooryck, C, Rötzer, KM, Ruiter, M, Sanlaville, D, Selmoni, S, Shen, Y, Siffredi, V, Thonney, J, Vallée, L, Van Binsbergen, E, Van der Aa, N, Van Haelst, MM, Vigneron, J, Vincent-Delorme, C, Vittoria, D, Vulto-Van Silfhout, AT, Witwicki, RM, Zwolinski, SA, Bowe, A, Beaudet, AL, Brewton, CM, Chu, Z, Dempsey, AG, Evans, YL, Garza, S, Kanne, SM, Laakman, AL, Lasala, MW, Llorens, AV, Marzano, G, Moss, TJ, Nowell, KP, Proud, MB, Chen, Q, Vaughan, R, Berman, J, Blaskey, L, Hines, K, Kessler, S, Khan, SY, Qasmieh, S, Bibb, AL, Paal, AM, Page, PZ, Smith-Packard, B, Buckner, R, Burko, J, Cavanagh, AL, Cerban, B, Snow, AV, Snyder, LAG, Keehn, RMN, Miller, DT, Miller, FK, Olson, JE, Triantafallou, C, Visyak, N, Atwell, C, Benedetti, M, Fischbach, GD, Greenup, M, Packer, A, Bukshpun, P, Cheong, M, Dale, C, Gobuty, SE, Hinkley, L, Jeremy, RJ, Lee, H, Luks, TL, Marco, EJ, Martin, AJ, McGovern, KE, Nagarajan, SS, Owen, J, Paul, BM, Pojman, NJ, Sinha, T, Swarnakar, V, Wakahiro, M, Alupay, H, Aaronson, B, Ackerman, S, Ankenman, K, Elgin, J, Gerdts, J, Johnson, K, Reilly, B, Shaw, D, Stevens, A, Ward, T, Wenegrat, J & Roberts, TPL 2012, 'A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders', Journal of Medical Genetics, vol. 49, no. 10, pp. 660-668. https://doi.org/10.1136/jmedgenet-2012-101203
TY - JOUR
T1 - A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders
AU - Zufferey, Flore
AU - Sherr, Elliott H.
AU - Beckmann, Noam D.
AU - Hanson, Ellen
AU - Maillard, Anne M.
AU - Hippolyte, Loyse
AU - Macé, Aurélien
AU - Ferrari, Carina
AU - Kutalik, Zoltán
AU - Andrieux, Joris
AU - Aylward, Elizabeth
AU - Barker, Mandy
AU - Bernier, Raphael
AU - Bouquillon, Sonia
AU - Conus, Philippe
AU - Delobel, Bruno
AU - Faucett, W. Andrew
AU - Goin-Kochel, Robin P.
AU - Grant, Ellen
AU - Harewood, Louise
AU - Hunter, Jill V.
AU - Lebon, Sébastien
AU - Ledbetter, David H.
AU - Martin, Christa Lese
AU - Männik, Katrin
AU - Martinet, Danielle
AU - Mukherjee, Pratik
AU - Ramocki, Melissa B.
AU - Spence, Sarah J.
AU - Steinman, Kyle J.
AU - Tjernage, Jennifer
AU - Spiro, John E.
AU - Reymond, Alexandre
AU - Beckmann, Jacques S.
AU - Chung, Wendy K.
AU - Jacquemont, Sébastien
AU - Addor, Marie Claude
AU - Arveiler, Benoit
AU - Belfiore, Marco
AU - Bena, Frédérique
AU - Bernardini, Laura
AU - Blanchet, Patricia
AU - Bonneau, Dominique
AU - Boute, Odile
AU - Callier, Patrick
AU - Campion, Dominique
AU - Chiesa, Jean
AU - Cordier, Marie Pierre
AU - Cuisset, Jean Marie
AU - David, Albert
AU - De Leeuw, Nicole
AU - De Vries, Bert
AU - Didelot, Gérard
AU - Doco-Fenzy, Martine
AU - Bedu, Bénédicte Duban
AU - Dubourg, Christèle
AU - Dupuis-Girod, Sophie
AU - Fagerberg, Christina R.
AU - Faivre, Laurence
AU - Fellmann, Florence
AU - Fernandez, Bridget A.
AU - Fisher, Richard
AU - Flori, Elisabeth
AU - Goldenberg, Alice
AU - Heron, Delphine
AU - Holder, Muriel
AU - Hoyer, Juliane
AU - Isidor, Bertrand
AU - Jaillard, Sylvie
AU - Jonveaux, Philippe
AU - Joriot, Sylvie
AU - Journel, Hubert
AU - Kooy, Frank
AU - le Caignec, Cédric
AU - Leheup, Bruno
AU - Lemaitre, Marie Pierre
AU - Lewis, Suzanne
AU - Malan, Valérie
AU - Mathieu-Dramard, Michèle
AU - Metspalu, Andres
AU - Morice-Picard, Fanny
AU - Mucciolo, Mafalda
AU - Oiglane-Shlik, Eve
AU - Ounap, Katrin
AU - Pasquier, Laurent
AU - Petit, Florence
AU - Philippe, Anne
AU - Plessis, Ghislaine
AU - Prieur, Fabienne
AU - Puechberty, Jacques
AU - Rajcan-Separovic, Evica
AU - Rauch, Anita
AU - Renieri, Alessandra
AU - Rieubland, Claudine
AU - Rooryck, Caroline
AU - Rötzer, Katharina Magdalena
AU - Ruiter, Mariken
AU - Sanlaville, Damien
AU - Selmoni, Stéphanie
AU - Shen, Yiping
AU - Siffredi, Vanessa
AU - Thonney, Jacques
AU - Vallée, Louis
AU - Van Binsbergen, Ellen
AU - Van der Aa, Nathalie
AU - Van Haelst, Mieke M.
AU - Vigneron, Jacqueline
AU - Vincent-Delorme, Catherine
AU - Vittoria, Disciglio
AU - Vulto-Van Silfhout, Anneke T.
AU - Witwicki, Robert M.
AU - Zwolinski, Simon A.
AU - Bowe, Alexandra
AU - Beaudet, Arthur L.
AU - Brewton, Christie M.
AU - Chu, Zili
AU - Dempsey, Allison G.
AU - Evans, Yolanda L.
AU - Garza, Silvia
AU - Kanne, Stephen M.
AU - Laakman, Anna L.
AU - Lasala, Morgan W.
AU - Llorens, Ashlie V.
AU - Marzano, Gabriela
AU - Moss, Timothy J.
AU - Nowell, Kerri P.
AU - Proud, Monica B.
AU - Chen, Qixuan
AU - Vaughan, Roger
AU - Berman, Jeffrey
AU - Blaskey, Lisa
AU - Hines, Katherine
AU - Kessler, Sudha
AU - Khan, Sarah Y.
AU - Qasmieh, Saba
AU - Bibb, Audrey Lynn
AU - Paal, Andrea M.
AU - Page, Patricia Z.
AU - Smith-Packard, Bethanny
AU - Buckner, Randy
AU - Burko, Jordan
AU - Cavanagh, Alyss Lian
AU - Cerban, Bettina
AU - Snow, Anne V.
AU - Snyder, Lee Anne Green
AU - Keehn, Rebecca Mc Nally
AU - Miller, David T.
AU - Miller, Fiona K.
AU - Olson, Jennifer Endre
AU - Triantafallou, Christina
AU - Visyak, Nicole
AU - Atwell, Constance
AU - Benedetti, Marta
AU - Fischbach, Gerald D.
AU - Greenup, Marion
AU - Packer, Alan
AU - Bukshpun, Polina
AU - Cheong, Maxwell
AU - Dale, Corby
AU - Gobuty, Sarah E.
AU - Hinkley, Leighton
AU - Jeremy, Rita J.
AU - Lee, Hana
AU - Luks, Tracy L.
AU - Marco, Elysa J.
AU - Martin, Alastair J.
AU - McGovern, Kathleen E.
AU - Nagarajan, Srikantan S.
AU - Owen, Julia
AU - Paul, Brianna M.
AU - Pojman, Nicholas J.
AU - Sinha, Tuhin
AU - Swarnakar, Vivek
AU - Wakahiro, Mari
AU - Alupay, Hanalore
AU - Aaronson, Benjamin
AU - Ackerman, Sean
AU - Ankenman, Katy
AU - Elgin, Jenna
AU - Gerdts, Jennifer
AU - Johnson, Kelly
AU - Reilly, Beau
AU - Shaw, Dennis
AU - Stevens, Arianne
AU - Ward, Tracey
AU - Wenegrat, Julia
AU - Roberts, Timothy P.L.
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84870280744&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870280744&partnerID=8YFLogxK
U2 - 10.1136/jmedgenet-2012-101203
DO - 10.1136/jmedgenet-2012-101203
M3 - Article
C2 - 23054248
AN - SCOPUS:84870280744
SN - 0022-2593
VL - 49
SP - 660
EP - 668
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
IS - 10
ER -
