title: Chromosomal microarray testing in adults with intellectual disability presenting with comorbid psychiatric disorders.
abstract: 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.
authors.affiliation: Division of Psychiatry, University College London, London, UK. k.wolfe@ucl.ac.uk.
authors.forename: Kate
authors.initials: K
authors.lastname: Wolfe
authors.affiliation: Division of Psychiatry, University College London, London, UK.
authors.forename: André
authors.initials: A
authors.lastname: Strydom
authors.affiliation: North East Thames Regional Genetics Service Laboratory, London, UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: Morrogh
authors.affiliation: North East Thames Regional Genetics Service Laboratory, London, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Carter
authors.affiliation: Nottinghamshire Healthcare NHS Foundation Trust, Nottingham, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Cutajar
authors.affiliation: Kent and Medway NHS and Social Care Partnership Trust, Kent, UK.
authors.forename: Mo
authors.initials: M
authors.lastname: Eyeoyibo
authors.affiliation: Division of Psychiatry, University College London, London, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Hassiotis
authors.affiliation: East London NHS Foundation Trust, London, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: McCarthy
authors.affiliation: Surrey and Borders Partnership NHS Foundation Trust, Surrey, UK.
authors.forename: Raja
authors.initials: R
authors.lastname: Mukherjee
authors.affiliation: Camden and Islington NHS Foundation Trust, London, UK.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Paschos
authors.affiliation: Cumbria Partnership NHS Foundation Trust, Cumbria, UK.
authors.forename: Nagarajan
authors.initials: N
authors.lastname: Perumal
authors.affiliation: South West Yorkshire Partnership NHS Foundation Trust, Yorkshire, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Read
authors.affiliation: Cornwall Partnership NHS Foundation Trust, Cornwall, UK.
authors.forename: Rohit
authors.identifier: http://orcid.org/0000-0002-1183-6933
authors.initials: R
authors.lastname: Shankar
authors.affiliation: Southern Health NHS Foundation Trust, Southampton, UK.
authors.forename: Saif
authors.initials: S
authors.lastname: Sharif
authors.affiliation: Coventry and Warwickshire Partnership NHS trust, Coventry, UK.
authors.forename: Suchithra
authors.initials: S
authors.lastname: Thirulokachandran
authors.affiliation: Division of Psychiatry, University College London, London, UK.
authors.forename: Johan H
authors.initials: JH
authors.lastname: Thygesen
authors.affiliation: Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Christine
authors.initials: C
authors.lastname: Patch
authors.affiliation: Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ogilvie
authors.affiliation: Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Frances
authors.initials: F
authors.lastname: Flinter
authors.affiliation: Division of Psychiatry, University College London, London, UK.
authors.forename: Andrew
authors.identifier: http://orcid.org/0000-0003-1567-2240
authors.initials: A
authors.lastname: McQuillin
authors.affiliation: Division of Psychiatry, University College London, London, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Bass
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000503:physiopathology; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002869:Chromosome Aberrations; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics; D004739:England; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D019006:Neural Cell Adhesion Molecules; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D044465:White People / Q000235:genetics
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C121001:NR2B NMDA receptor; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D016194:Receptors, N-Methyl-D-Aspartate