Clinical Genetic Testing for Patients With Autism Spectrum Disorders
Top Cited Papers
- 1 April 2010
- journal article
- research article
- Published by American Academy of Pediatrics (AAP) in PEDIATRICS
- Vol. 125 (4), e727-e735
- https://doi.org/10.1542/peds.2009-1684
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.Keywords
This publication has 42 references indexed in Scilit:
- Recurrent Rearrangements of Chromosome 1q21.1 and Variable Pediatric PhenotypesThe New England Journal of Medicine, 2008
- Breakpoint Mapping and Array CGH in Translocations: Comparison of a Phenotypically Normal and an Abnormal CohortAmerican Journal of Human Genetics, 2008
- Clinical genetics evaluation in identifying the etiology of autism spectrum disordersGenetics in Medicine, 2008
- The Fine-Scale and Complex Architecture of Human Copy-Number VariationAmerican Journal of Human Genetics, 2008
- A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizuresNature Genetics, 2008
- Structural Variation of Chromosomes in Autism Spectrum DisorderAmerican Journal of Human Genetics, 2008
- Diagnostic Stability in Very Young Children with Autism Spectrum DisordersJournal of Autism and Developmental Disorders, 2007
- A unified genetic theory for sporadic and inherited autismProceedings of the National Academy of Sciences of the United States of America, 2007
- Strong Association of De Novo Copy Number Mutations with AutismScience, 2007
- Global variation in copy number in the human genomeNature, 2006