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
