The psychiatric phenotypes of 1q21 distal deletion and duplication
Open Access
- 4 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Translational Psychiatry
- Vol. 11 (1), 1-10
- https://doi.org/10.1038/s41398-021-01226-9
Abstract
Copy number variants are amongst the most highly penetrant risk factors for psychopathology and neurodevelopmental deficits, but little information about the detailed clinical phenotype associated with particular variants is available. We present the largest study of the microdeletion and -duplication at the distal 1q21 locus, which has been associated with schizophrenia and intellectual disability, in order to investigate the range of psychiatric phenotypes. Clinical and cognitive data from 68 deletion and 55 duplication carriers were analysed with logistic regression analysis to compare frequencies of mental disorders between carrier groups and controls, and linear mixed models to compare quantitative phenotypes. Both children and adults with copy number variants at 1q21 had high frequencies of psychopathology. In the children, neurodevelopmental disorders were most prominent (56% for deletion, 68% for duplication carriers). Adults had increased prevalence of mood (35% for deletion [OR=6.6 (95% CI: 1.4-40.1)], 55% for duplication carriers [8.3 (1.4-55.5)]) and anxiety disorders (24% [1.8 (0.4-8.4)] and 55% [10.0 (1.9-71.2)]). The adult group, which included mainly genetically affected parents of probands, had an IQ in the normal range. These results confirm high prevalence of neurodevelopmental disorders associated with CNVs at 1q21 but also reveal high prevalence of mood and anxiety disorders in a high-functioning adult group with these CNVs. Because carriers of neurodevelopmental CNVs who show relevant psychopathology but no major cognitive impairment are not currently routinely receiving clinical genetic services widening of genetic testing in psychiatry may be considered.Funding Information
- RCUK | Medical Research Council
- Wellcome Trust
- Waterloo Foundation
- Health and Care Research Wales
- Simons Foundation
This publication has 38 references indexed in Scilit:
- 1q21.1 Microduplication expression in adultsGenetics in Medicine, 2013
- A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disordersJournal of Medical Genetics, 2012
- DUF1220-Domain Copy Number Implicated in Human Brain-Size Pathology and EvolutionAmerican Journal of Human Genetics, 2012
- Simons Variation in Individuals Project (Simons VIP): A Genetics-First Approach to Studying Autism Spectrum and Related Neurodevelopmental DisordersNeuron, 2012
- Psychometric Properties of the Revised Developmental Coordination Disorder QuestionnairePhysical & Occupational Therapy In Pediatrics, 2009
- Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalitiesNature Genetics, 2008
- Recurrent Rearrangements of Chromosome 1q21.1 and Variable Pediatric PhenotypesThe New England Journal of Medicine, 2008
- Prodromal Assessment With the Structured Interview for Prodromal Syndromes and the Scale of Prodromal Symptoms: Predictive Validity, Interrater Reliability, and Training to ReliabilitySchizophrenia Bulletin, 2003
- Diagnostic Interview for Genetic StudiesArchives of General Psychiatry, 1994
- Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disordersJournal of Autism and Developmental Disorders, 1994