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Neuropediatrics 2019; 50(06): 367-377
DOI: 10.1055/s-0039-1694797
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Identification of Copy Number Variation by Array-CGH in Portuguese Children and Adolescents Diagnosed with Autism Spectrum Disorders

S. Monteiro
1   Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal
2   MMED, Master's Degree in Medicine, University of Porto, Porto, Portugal
,
J. Pinto
1   Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal
3   i3S – Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
,
A. Mira Coelho
4   Department of Child Psychiatry Consultation, Centro hospitalar de São João (CHSJ) Porto, Porto, Portugal
,
M. Leão
1   Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal
5   Department of Neurogenetic Consultation, Centro hospitalar de São João (CHSJ) Porto, Porto, Portugal
,
S. Dória 
1   Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal
3   i3S – Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal
› Author Affiliations
Further Information

Publication History

11 March 2019

01 July 2019

Publication Date:
09 August 2019 (online)

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Abstract

Background Autism spectrum disorders (ASD) affect many children with an estimated prevalence of 1%. Array-comparative genomic hybridization (CGH) offers significant sensitivity for the identification of submicroscopic chromosomal abnormalities and it is one of the most used techniques in daily practice. The main objective of this study was to describe the usefulness of array-CGH in the etiologic diagnosis of ASD.

Methods Two-hundred fifty-three patients admitted to a neurogenetic outpatient clinic and diagnosed with ASD were selected for array-CGH (4 × 180K microarrays). Public databases were used for classification in accordance with the American College of Medical Genetics Standards and Guidelines.

Results About 3.56% (9/253) of copy number variations (CNVs) were classified as pathogenic. When likely pathogenic CNVs were considered, the rate increased to 11.46% (29/253). Some CNVs apparently not correlated to the ASD were also found. Considering a phenotype–genotype correlation, the patients were divided in two groups. One group according to previous literature includes all the CNVs related to ASDs (23 CNVs present in 22 children) and another with those apparently not related to ASD (10 CNVs present in 7 children). In 18 patients, a next-generation sequencing (NGS) panel were performed. From these, one pathogenic and 16 uncertain significance variants were identified.

Conclusion The results of our study are in accordance with the literature, highlighting the relevance of array-CGH in the genetic of diagnosis of ASD population, namely when associated with other features. Our study also reinforces the need for complementarity between array-CGH and NGS panels or whole exome sequencing in the etiological diagnosis of ASD.

Keywords

array-comparative genomic hybridization - copy number variation - next-generation sequencing - autistic spectrum disorders
 

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