PT  - JOURNAL ARTICLE
AU  - Shen, Yiping
AU  - Dies, Kira A.
AU  - Holm, Ingrid A.
AU  - Bridgemohan, Carolyn
AU  - Sobeih, Magdi M.
AU  - Caronna, Elizabeth B.
AU  - Miller, Karen J.
AU  - Frazier, Jean A.
AU  - Silverstein, Iris
AU  - Picker, Jonathan
AU  - Weissman, Laura
AU  - Raffalli, Peter
AU  - Jeste, Shafali
AU  - Demmer, Laurie A.
AU  - Peters, Heather K.
AU  - Brewster, Stephanie J.
AU  - Kowalczyk, Sara J.
AU  - Rosen-Sheidley, Beth
AU  - McGowan, Caroline
AU  - Duda, Andrew W.
AU  - Lincoln, Sharyn A.
AU  - Lowe, Kathryn R.
AU  - Schonwald, Alison
AU  - Robbins, Michael
AU  - Hisama, Fuki
AU  - Wolff, Robert
AU  - Becker, Ronald
AU  - Nasir, Ramzi
AU  - Urion, David K.
AU  - Milunsky, Jeff M.
AU  - Rappaport, Leonard
AU  - Gusella, James F.
AU  - Walsh, Christopher A.
AU  - Wu, Bai-Lin
AU  - Miller, David T.
AU  - , 
TI  - Clinical Genetic Testing for Patients With Autism Spectrum Disorders
AID  - 10.1542/peds.2009-1684
DP  - 2010 Apr 01
TA  - Pediatrics
PG  - e727--e735
VI  - 125
IP  - 4
4099  - http://pediatrics.aappublications.org/content/125/4/e727.short
4100  - http://pediatrics.aappublications.org/content/125/4/e727.full
SO  - Pediatrics2010 Apr 01; 125
AB  - 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.