Clinical genetic testing for patients with autism spectrum disorders.
Pediatrics
; 125(4): e727-35, 2010 Apr.
Article
en En
| MEDLINE
| ID: mdl-20231187
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 ANDMETHODS:
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Trastornos Generalizados del Desarrollo Infantil
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Pruebas Genéticas
Tipo de estudio:
Etiology_studies
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Guideline
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Pediatrics
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos