Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder

The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study. To perform chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic y...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	JAMA : the journal of the American Medical Association Ročník 314; číslo 9; s. 895
Hlavní autori:	Tammimies, Kristiina, Marshall, Christian R, Walker, Susan, Kaur, Gaganjot, Thiruvahindrapuram, Bhooma, Lionel, Anath C, Yuen, Ryan K C, Uddin, Mohammed, Roberts, Wendy, Weksberg, Rosanna, Woodbury-Smith, Marc, Zwaigenbaum, Lonnie, Anagnostou, Evdokia, Wang, Zhuozhi, Wei, John, Howe, Jennifer L, Gazzellone, Matthew J, Lau, Lynette, Sung, Wilson W L, Whitten, Kathy, Vardy, Cathy, Crosbie, Victoria, Tsang, Brian, D'Abate, Lia, Tong, Winnie W L, Luscombe, Sandra, Doyle, Tyna, Carter, Melissa T, Szatmari, Peter, Stuckless, Susan, Merico, Daniele, Stavropoulos, Dimitri J, Scherer, Stephen W, Fernandez, Bridget A
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 01.09.2015
Predmet:	Asperger Syndrome - diagnosis Asperger Syndrome - genetics Autistic Disorder - diagnosis Autistic Disorder - genetics Child Child Development Disorders, Pervasive - diagnosis Child Development Disorders, Pervasive - genetics Child Development Disorders, Pervasive - pathology Child, Preschool Exome Female Humans Male Microarray Analysis - methods Microarray Analysis - statistics & numerical data Molecular Diagnostic Techniques - methods Molecular Diagnostic Techniques - statistics & numerical data Mutation Oligonucleotide Array Sequence Analysis - statistics & numerical data Phenotype Sequence Analysis, DNA - methods Sequence Analysis, Protein - methods
ISSN:	1538-3598, 1538-3598
On-line prístup:	Zistit podrobnosti o prístupe
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Popis
Shrnutí:	The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study. To perform chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic yield of these tests in a sample typical of a developmental pediatric clinic. The sample consisted of 258 consecutively ascertained unrelated children with ASD who underwent detailed assessments to define morphology scores based on the presence of major congenital abnormalities and minor physical anomalies. The children were recruited between 2008 and 2013 in Newfoundland and Labrador, Canada. The probands were stratified into 3 groups of increasing morphological severity: essential, equivocal, and complex (scores of 0-3, 4-5, and ≥6). All probands underwent CMA, with WES performed for 95 proband-parent trios. The overall molecular diagnostic yield for CMA and WES in a population-based ASD sample stratified in 3 phenotypic groups. Of 258 probands, 24 (9.3%, 95%CI, 6.1%-13.5%) received a molecular diagnosis from CMA and 8 of 95 (8.4%, 95%CI, 3.7%-15.9%) from WES. The yields were statistically different between the morphological groups. Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic etiology was 15.8% (95%CI, 9.1%-24.7%; 15/95 children). This included 2 children who received molecular diagnoses from both tests. The combined yield was significantly higher in the complex group when compared with the essential group (pairwise comparison, P = .002). [table: see text]. Among a heterogeneous sample of children with ASD, the molecular diagnostic yields of CMA and WES were comparable, and the combined molecular diagnostic yield was higher in children with more complex morphological phenotypes in comparison with the children in the essential category. If replicated in additional populations, these findings may inform appropriate selection of molecular diagnostic testing for children affected by ASD.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1538-3598 1538-3598
DOI:	10.1001/jama.2015.10078