Dosage of copy number variation at 22q11.2 mediates changes in cognition, social function and brain structure in autism spectrum disorder

Hsin-I Chen; Yi-Ling Chien; Hsio-Mei Liao; Wei-Hsien Chien; Chia-Hsiang Chen; Yu-Chieh Chen; Susan Shur-Fen Gau

doi:10.1016/j.jfma.2016.02.005

Dosage of copy number variation at 22q11.2 mediates changes in cognition, social function and brain structure in autism spectrum disorder

J Formos Med Assoc. 2016 Jul;115(7):577-82. doi: 10.1016/j.jfma.2016.02.005. Epub 2016 Mar 26.

Authors

Hsin-I Chen¹, Yi-Ling Chien¹, Hsio-Mei Liao¹, Wei-Hsien Chien², Chia-Hsiang Chen³, Yu-Chieh Chen⁴, Susan Shur-Fen Gau⁵

Affiliations

¹ Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
² Department of Occupational Therapy, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
³ Department of Psychiatry, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan.
⁴ Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan.
⁵ Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: gaushufe@ntu.edu.tw.

PMID: 27026301
DOI: 10.1016/j.jfma.2016.02.005

Abstract

Microdeletion at 22q11.2, a common copy number variation (CNV) noted in neurodevelopmental disorders, may be associated with cognitive impairment. However, cognitive function in individuals with microduplication remains unclear. This work presents the genetic, clinical, and brain structural data of two men out of 335 probands with autistic spectrum disorder (ASD) who had different CNV dosages at 22q11.2, and comparison with their siblings, 55 ASD probands, and 73 controls. Both showed severe autistic symptoms, but the proband with microduplication demonstrated better cognitive functions. Furthermore, different cingulate gyrus volume changes were noted, indicating that the proband with 22q11.2 microduplication had a different pattern of cingulate gyrus structure. Our comprehensive characterization of the behavioral, cognitive, and imaging phenotypes of ASD probands with different CNV dosage at 22q11.2 contribute to how copy number changes at 22q11.2 mediate the phenotypes in ASD, and pave the way for future clinical and functional study on these variants.

Keywords: 22q11.2; brain structure; cognition; copy number variation; social function.

MeSH terms

22q11 Deletion Syndrome / complications*
Adolescent
Autism Spectrum Disorder / genetics*
Autism Spectrum Disorder / psychology*
Child
Child, Preschool
Cognition
DNA Copy Number Variations*
Female
Gyrus Cinguli / diagnostic imaging
Humans
Male
Phenotype
Taiwan