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Cited by 394Genomic variations and chromosomal abnormalitiesAutism Spectrum Disorder ResearchGenomics and Rare Diseases

Clinical Genetic Testing for Patients With Autism Spectrum Disorders

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Shen, Yiping, Dies, Kira A., Holm, Ingrid A., Bridgemohan, Carolyn, Sobeih, Magdi M., Caronna, Elizabeth B., Miller, Karen J., Frazier, Jean A. +28 more·2010·Pediatrics
DOI 10.1542/peds.2009-1684PMC PMC4247857
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Abstract

BACKGROUND: Multiple lines of evidence indicate a strong genetic contribution to autism spectrum disorders (ASDs). Current guidelines for clinical genetic testing recommend a G-banded karyotype to detect chromosomal abnormalities and fragile X DNA testing, but guidelines for chromosomal microarray analysis have not been established. PATIENTS AND METHODS: A cohort of 933 patients received clinical genetic testing for a diagnosis of ASD between January 2006 and December 2008. Clinical genetic testing included G-banded karyotype, fragile X testing, and chromosomal microarray (CMA) to test for submicroscopic genomic deletions and duplications. Diagnostic yield of clinically significant genetic changes was compared. RESULTS: Karyotype yielded abnormal results in 19 of 852 patients (2.23% [95% confidence interval (CI): 1.73%–2.73%]), fragile X testing was abnormal in 4 of 861 (0.46% [95% CI: 0.36%–0.56%]), and CMA identified deletions or duplications in 154 of 848 patients (18.2% [95% CI: 14.76%–21.64%]). CMA results for 59 of 848 patients (7.0% [95% CI: 5.5%–8.5%]) were considered abnormal, which includes variants associated with known genomic disorders or variants of possible significance. CMA results were normal in 10 of 852 patients (1.2%) with abnormal karyotype due to balanced rearrangements or unidentified marker chromosome. CMA with whole-genome coverage and CMA with targeted genomic regions detected clinically relevant copy-number changes in 7.3% (51 of 697) and 5.3% (8 of 151) of patients, respectively, both higher than karyotype. With the exception of recurrent deletion and duplication of chromosome 16p11.2 and 15q13.2q13.3, most copy-number changes were unique or identified in only a small subset of patients. CONCLUSIONS: CMA had the highest detection rate among clinically available genetic tests for patients with ASD. Interpretation of microarray data is complicated by the presence of both novel and recurrent copy-number variants of unknown significance. Despite these limitations, CMA should be considered as part of the initial diagnostic evaluation of patients with ASD.

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  • More than 200 autism susceptibility genes have been identified to date, and complex patterns of inheritance, such as oligogenic heterozygosity, appear to contribute to the etiopathogenesis of autism.

    “Thus, more than 200 autism susceptibility genes have been identified to date, and complex patterns of inheritance, such as oligogenic heterozygosity, appear to contribute to the etiopathogenesis of autism.”

    From Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms (2014) · cites this paper as [2]

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  1. [16]Shevell M Ashwal S Donley D Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society Neurology 2003 60 3 367 380 12578916

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Authors
Shen, Y., Dies, K. A., Holm, I. A., Bridgemohan, C., Sobeih, M. M., Caronna, E. B., Miller, K. J., Frazier, J. A., Silverstein, I., Picker, J., Weissman, L., Raffalli, P., Jeste, S., Demmer, L. A., Peters, H. K., Brewster, S. J., Kowalczyk, S. J., Rosen-Sheidley, B., McGowan, C., Duda, A. W., Lincoln, S. A., Lowe, K. R., Schonwald, A., Robbins, M., Hisama, F., Wolff, R., Becker, R., Nasir, R., Urion, D. K., Milunsky, J. M., Rappaport, L., Gusella, J. F., Walsh, C. A., Wu, B.-L., Miller, D. T., & on behalf of the Autism Consortium Clinical Genetics/DNA Diagnostics Collaboration
Affiliations
  • Harvard University (US)
  • Autism Consortium (US)
  • Tufts Medical Center (US)
  • University of Massachusetts Chan Medical School (US)
  • Boston Children's Hospital (US)
  • Autism Consortium, Boston, Massachusetts;
  • Boston University (US)
  • Shanghai Medical College of Fudan University (CN)
ORCID
Venue
Pediatrics
Publisher
American Academy of Pediatrics (AAP)
Published
2010-04-01
Volume
125
Issue
4
Pages
e727-e735
ISSN
  • 0031-4005 (ISSN-L)
  • 1098-4275
DOI
10.1542/peds.2009-1684
PMC
PMC4247857
OpenAlex
W2114107709
Cited by
394
References
40
Citations by year
2026: 3 · 2025: 5 · 2024: 14 · 2023: 11 · 2022: 15 · 2021: 21 · 2020: 20 · 2019: 22 · 2018: 27 · 2017: 26 · 2016: 22 · 2015: 25 · 2014: 35 · 2013: 40 · 2012: 55
FWCI
26.24
Type
journal article
Language
en
Open access
Locations
  • PEDIATRICS (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • Autism Speaks (AS2042)
  • Children's Tumor Foundation
  • Nancy Lurie Marks Family Foundation
  • Fudan University
  • National Center for Research Resources (UL1RR025758)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords
autism spectrum disorder, clinical genetic testing, chromosomal microarray analysis, copy number variation, diagnostic yield, variants of uncertain significance, chromosome 16p11.2, chromosomal abnormalities
MeSH terms
Adolescent, Child, Child Development Disorders, Pervasive, Child, Preschool, Female, Genetic Testing, Humans, Infant, Karyotyping, Male, Cohort Studies, Microarray Analysis, Young Adult

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