TY - JOUR
T1 - Chromosomal microarray testing in adults with intellectual disability presenting with comorbid psychiatric disorders
AU - Wolfe, Kate
AU - Strydom, André
AU - Morrogh, Deborah
AU - Carter, Jennifer
AU - Cutajar, Peter
AU - Eyeoyibo, Mo
AU - Hassiotis, Angela
AU - McCarthy, Jane
AU - Mukherjee, Raja
AU - Paschos, Dimitrios
AU - Perumal, Nagarajan
AU - Read, Stephen
AU - Shankar, Rohit
AU - Sharif, Saif
AU - Thirulokachandran, Suchithra
AU - Thygesen, Johan H
AU - Patch, Christine
AU - Ogilvie, Caroline
AU - Flinter, Frances
AU - McQuillin, Andrew
AU - Bass, Nick
PY - 2016/9/21
Y1 - 2016/9/21
N2 - Chromosomal copy-number variations (CNVs) are a class of genetic variants highly implicated in the aetiology of neurodevelopmental disorders, including intellectual disabilities (ID), schizophrenia and autism spectrum disorders (ASD). Yet the majority of adults with idiopathic ID presenting to psychiatric services have not been tested for CNVs. We undertook genome-wide chromosomal microarray analysis (CMA) of 202 adults with idiopathic ID recruited from community and in-patient ID psychiatry services across England. CNV pathogenicity was assessed using standard clinical diagnostic methods and participants underwent comprehensive medical and psychiatric phenotyping. We found an 11% yield of likely pathogenic CNVs (22/202). CNVs at recurrent loci, including the 15q11-q13 and 16p11.2-p13.11 regions were most frequently observed. We observed an increased frequency of 16p11.2 duplications compared with those reported in single-disorder cohorts. CNVs were also identified in genes known to effect neurodevelopment, namely NRXN1 and GRIN2B. Furthermore deletions at 2q13, 12q21.2-21.31 and 19q13.32, and duplications at 4p16.3, 13q32.3-33.3 and Xq24-25 were observed. Routine CMA in ID psychiatry could uncover ~11% new genetic diagnoses with potential implications for patient management. We advocate greater consideration of CMA in the assessment of adults with idiopathic ID presenting to psychiatry services.European Journal of Human Genetics advance online publication, 21 September 2016; doi:10.1038/ejhg.2016.107.
AB - Chromosomal copy-number variations (CNVs) are a class of genetic variants highly implicated in the aetiology of neurodevelopmental disorders, including intellectual disabilities (ID), schizophrenia and autism spectrum disorders (ASD). Yet the majority of adults with idiopathic ID presenting to psychiatric services have not been tested for CNVs. We undertook genome-wide chromosomal microarray analysis (CMA) of 202 adults with idiopathic ID recruited from community and in-patient ID psychiatry services across England. CNV pathogenicity was assessed using standard clinical diagnostic methods and participants underwent comprehensive medical and psychiatric phenotyping. We found an 11% yield of likely pathogenic CNVs (22/202). CNVs at recurrent loci, including the 15q11-q13 and 16p11.2-p13.11 regions were most frequently observed. We observed an increased frequency of 16p11.2 duplications compared with those reported in single-disorder cohorts. CNVs were also identified in genes known to effect neurodevelopment, namely NRXN1 and GRIN2B. Furthermore deletions at 2q13, 12q21.2-21.31 and 19q13.32, and duplications at 4p16.3, 13q32.3-33.3 and Xq24-25 were observed. Routine CMA in ID psychiatry could uncover ~11% new genetic diagnoses with potential implications for patient management. We advocate greater consideration of CMA in the assessment of adults with idiopathic ID presenting to psychiatry services.European Journal of Human Genetics advance online publication, 21 September 2016; doi:10.1038/ejhg.2016.107.
U2 - 10.1038/ejhg.2016.107
DO - 10.1038/ejhg.2016.107
M3 - Article
C2 - 27650969
SN - 1018-4813
JO - European journal of human genetics : EJHG
JF - European journal of human genetics : EJHG
ER -