Clinical genetic testing for patients with autism spectrum disorders - PubMed (original) (raw)

Comparative Study

. 2010 Apr;125(4):e727-35.

doi: 10.1542/peds.2009-1684. Epub 2010 Mar 15.

Kira A Dies, Ingrid A Holm, Carolyn Bridgemohan, Magdi M Sobeih, Elizabeth B Caronna, Karen J Miller, Jean A Frazier, Iris Silverstein, Jonathan Picker, Laura Weissman, Peter Raffalli, Shafali Jeste, Laurie A Demmer, Heather K Peters, Stephanie J Brewster, Sara J Kowalczyk, Beth Rosen-Sheidley, Caroline McGowan, Andrew W Duda 3rd, Sharyn A Lincoln, Kathryn R Lowe, Alison Schonwald, Michael Robbins, Fuki Hisama, Robert Wolff, Ronald Becker, Ramzi Nasir, David K Urion, Jeff M Milunsky, Leonard Rappaport, James F Gusella, Christopher A Walsh, Bai-Lin Wu, David T Miller; Autism Consortium Clinical Genetics/DNA Diagnostics Collaboration

Collaborators, Affiliations

Comparative Study

Clinical genetic testing for patients with autism spectrum disorders

Yiping Shen et al. Pediatrics. 2010 Apr.

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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