Clinical and molecular characterization of three genomic rearrangements at chromosome 22q13.3 associated with autism spectrum disorder

Chia Hsiang Chen, Hsin I. Chen, Hsiao Mei Liao, Yann Jang Chen, Jye Siung Fang, Kuei Fang Lee, Susan Shur Fen Gau*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Objectives Chromosome 22q13 is a hot region of genomic rearrangements that may result in deletion, duplication, and translocation, and that may lead to neurodevelopmental disorders in affected patients. Materials and methods We carried out an array-based comparative genomic hybridization analysis to detect copy number variations (CNVs) of genomic DNA in patients with autism spectrum disorders (ASD) who were consecutively recruited into our molecular genetic study of ASD. Karyotyping, fluorescent in-situ hybridization analysis, and real time-quantitative PCR were used for validation tests. Results We completed a genome-wide CNV analysis of 335 patients with ASD from Taiwan. Three unrelated male patients were found to carry three different CNVs at 22q13.3, respectively, including a de novo terminal deletion of ~106 kb at 22q13.33, a de novo interstitial duplication of ~1.8Mb at 22q13.32-q13.33, and a microdeletion of ~147 kb at 22q13.33. These three CNVs all involved the dosage change of the SHANK3 gene. The last patient also carried a genomic duplication of ~3.86Mb at 19q13.42-q13.4 in addition to a microdeletion of ~147 kb at 22q13.33. His younger sister also carried these two CNVs, but she had developmental delay and other neurological deficits without ASD. These two CNVs were transmitted from their unaffected father, who carried a balanced translocation between chromosome 22q and 19q. Conclusion Our data support that recurrent genomic rearrangements at 22q13.3 are part of the genetic landscape of ASD in our patients and changes in SHANK3 dosage are associated with neurodevelopmental disorders. However, the clinical symptoms of patients with 22q13.3 rearrangements can vary depending on other genetic and nongenetic factors, not limited to genes involved in CNVs in this region. Psychiatr Genet 27:23-33 Copyright . 2017 Wolters Kluwer Health, Inc. All rights reserved.

Original languageEnglish
Pages (from-to)23-33
Number of pages11
JournalPsychiatric Genetics
Issue number1
StatePublished - 2017


  • 22q13
  • Autism spectrum disorder
  • Chromosomal translocation
  • Copy number variation
  • SHANK3


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