Identification and molecular characterization of two novel chromosomal deletions associated with autism

Authors

  • W-H Chien,

    1. Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan
    Search for more papers by this author
  • SS-F Gau,

    Corresponding author
    1. Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan
    2. Department of Psychiatry, National Taiwan University College of Medicine, Taipei, Taiwan
    • Susan Shur-Fen Gau, MD, PhD, Department of Psychiatry, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan South Road, Taipei 10002, Taiwan. Tel.: +886 2 23123456x66802; fax: +886 2 23812408;
      e-mail: gaushufe@ntu.edu.tw

      Dr Chia-Hsiang Chen, MD, PhD, Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, 350 Taiwan. Tel.: +886 37 246166x36713; fax: +886 37 586453;
      e-mail: cchen@nhri.org.tw

    Search for more papers by this author
  • Y-Y Wu,

    1. Department of Psychiatry, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Tao-Yuan, Taiwan
    Search for more papers by this author
  • Y-S Huang,

    1. Department of Psychiatry, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Tao-Yuan, Taiwan
    Search for more papers by this author
  • J-S Fang,

    1. Graduate Institute of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien, Taiwan
    Search for more papers by this author
  • Y-J Chen,

    1. Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan
    2. Department of Teaching and Research, Taipei City Hospital, Taipei, Taiwan
    Search for more papers by this author
  • W-T Soong,

    1. Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan
    2. St. Joseph's Hospital, Yunlin County, Taiwan
    Search for more papers by this author
  • Y-N Chiu,

    1. Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan
    Search for more papers by this author
  • C-H Chen

    Corresponding author
    1. Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan
    2. Department of Psychiatry, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University College of Medicine, Tao-Yuan, Taiwan
    3. Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
    • Susan Shur-Fen Gau, MD, PhD, Department of Psychiatry, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan South Road, Taipei 10002, Taiwan. Tel.: +886 2 23123456x66802; fax: +886 2 23812408;
      e-mail: gaushufe@ntu.edu.tw

      Dr Chia-Hsiang Chen, MD, PhD, Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, 350 Taiwan. Tel.: +886 37 246166x36713; fax: +886 37 586453;
      e-mail: cchen@nhri.org.tw

    Search for more papers by this author

Abstract

Chien W-H, Gau SS-F, Wu Y-Y, Huang Y-S, Fang J-S, Chen Y-J, Soong W-T, Chiu Y-N, Chen C-H. Identification and molecular characterization of two novel chromosomal deletions associated with autism.

Autism is a childhood-onset neurodevelopmental disorder with a strong genetic basis in its etiology. Conventional karyotype analysis has revealed that chromosomal structural aberrations such as translocation, inversion, deletion, and duplication play a role in causing autism spectrum disorders (ASD). In addition, recent array-based comparative genomic hybridization (array CGH) studies discovered that submicroscopic deletion and duplication of DNA segments also contributed significantly to the genetic etiology of ASD. Together, these studies indicate that genomic rearrangement is an important genetic mechanism of ASD. Using karyotyping analysis and array CGH technology, we identified a subtelomeric deletion of approximately 6.8 Mb at 4q35.1-35.2 and a terminal deletion of approximately 2.4 Mb at 8p23.2-pter in two autistic boys, respectively. These two deletions were further validated using fluorescent in situ hybridization and real-time quantitative polymerase chain reaction, and their breakpoints were delineated using high-resolution array CGH. The 4q deletion is a rare de novo mutation, while the transmission of 8p deletion is unknown, because the father of the patient was unavailable for study. These two deletions are rare mutations and were not found in the additional 282 patients with ASD and in the 300 control subjects in our population. The identification of these two chromosomal deletions contribute to our understanding of the genetic basis of ASD, and the haploinsufficiency of several genes located at the deleted regions of chromosome 8p and 4q may contribute to the clinical phenotypes of autism.

Ancillary