TY - JOUR
T1 - Delineating the psychiatric and behavioral phenotype of recurrent 2q13 deletions and duplications
AU - Wolfe, Kate
AU - McQuillin, Andrew
AU - Alesi, Viola
AU - Boudry Labis, Elise
AU - Cutajar, Peter
AU - Dallapiccola, Bruno
AU - Dentici, Maria Lisa
AU - Dieux-Coeslier, Anne
AU - Duban-Bedu, Benedicte
AU - Duelund Hjortshøj, Tina
AU - Goel, Himanshu
AU - Loddo, Sara
AU - Morrogh, Deborah
AU - Mosca-Boidron, Anne-Laure
AU - Novelli, Antonio
AU - Olivier-Faivre, Laurence
AU - Parker, Jennifer
AU - Parker, Michael J
AU - Patch, Christine
AU - Pelling, Anna L
AU - Smol, Thomas
AU - Tümer, Zeynep
AU - Vanakker, Olivier
AU - van Haeringen, Arie
AU - Vanlerberghe, Clémence
AU - Strydom, Andre
AU - Skuse, David
AU - Bass, Nick
PY - 2018/6
Y1 - 2018/6
N2 - Recurrent deletions and duplications at the 2q13 locus have been associated with developmental delay (DD) and dysmorphisms. We aimed to undertake detailed clinical characterization of individuals with 2q13 copy number variations (CNVs), with a focus on behavioral and psychiatric phenotypes. Participants were recruited via the Unique chromosomal disorder support group, U.K. National Health Service Regional Genetics Centres, and the DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources (DECIPHER) database. A review of published 2q13 patient case reports was undertaken to enable combined phenotypic analysis. We present a new case series of 2q13 CNV carriers (21 deletion, 4 duplication) and the largest ever combined analysis with data from published studies, making a total of 54 deletion and 23 duplication carriers. DD/intellectual disabilities was identified in the majority of carriers (79% deletion, 70% duplication), although in the new cases 52% had an IQ in the borderline or normal range. Despite the median age of the new cases being only 9 years, 64% had a clinical psychiatric diagnosis. Combined analysis found attention deficit hyperactivity disorder (ADHD) to be the most frequent diagnosis (48% deletion, 60% duplication), followed by autism spectrum disorders (33% deletion, 17% duplication). Aggressive (33%) and self-injurious behaviors (33%) were also identified in the new cases. CNVs at 2q13 are typically associated with DD with mildly impaired intelligence, and a high rate of childhood psychiatric diagnoses-particularly ADHD. We have further characterized the clinical phenotype related to imbalances of the 2q13 region and identified it as a region of interest for the neurobiological investigation of ADHD.
AB - Recurrent deletions and duplications at the 2q13 locus have been associated with developmental delay (DD) and dysmorphisms. We aimed to undertake detailed clinical characterization of individuals with 2q13 copy number variations (CNVs), with a focus on behavioral and psychiatric phenotypes. Participants were recruited via the Unique chromosomal disorder support group, U.K. National Health Service Regional Genetics Centres, and the DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources (DECIPHER) database. A review of published 2q13 patient case reports was undertaken to enable combined phenotypic analysis. We present a new case series of 2q13 CNV carriers (21 deletion, 4 duplication) and the largest ever combined analysis with data from published studies, making a total of 54 deletion and 23 duplication carriers. DD/intellectual disabilities was identified in the majority of carriers (79% deletion, 70% duplication), although in the new cases 52% had an IQ in the borderline or normal range. Despite the median age of the new cases being only 9 years, 64% had a clinical psychiatric diagnosis. Combined analysis found attention deficit hyperactivity disorder (ADHD) to be the most frequent diagnosis (48% deletion, 60% duplication), followed by autism spectrum disorders (33% deletion, 17% duplication). Aggressive (33%) and self-injurious behaviors (33%) were also identified in the new cases. CNVs at 2q13 are typically associated with DD with mildly impaired intelligence, and a high rate of childhood psychiatric diagnoses-particularly ADHD. We have further characterized the clinical phenotype related to imbalances of the 2q13 region and identified it as a region of interest for the neurobiological investigation of ADHD.
U2 - 10.1002/ajmg.b.32627
DO - 10.1002/ajmg.b.32627
M3 - Journal article
C2 - 29603867
SN - 1552-4841
VL - 177
SP - 397
EP - 405
JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
IS - 4
ER -