Dados do Trabalho

Título

COPY NUMBER VARIATION FINDINGS BY CHROMOSOMAL MICROARRAY ANALYSIS OF 100 INDIVIDUALS WITH AUTISM SPECTRUM DISORDERS.

Introdução

Autism spectrum disorders (ASD) is a heterogeneous group of neurodevelopmental disorder with a prevalence of ~1% in the general population. Genetics plays an important role in the etiology of ASD, and the rare variants are the ones that confer a higher risk for an individual. Chromosomal microarray analysis (CMA) is a robust technique recommended in the evaluation of ASD.

Objetivo

Here we present data of our experience using CMA to evaluate the prevalence of copy number variation (CNVs) in ASD individuals referred by neurologists, pediatricians, and clinical geneticists. We evaluated 100 unrelated consecutive individuals in our routine cohort from January to March 2023, presenting with ASD. The extracted DNA was submitted to CGH-array 400K (Agilent) protocol. The samples were analyzed using CytoGenomics and Alissa softwares (Agilent). The interpretation and reports were performed by two independent analysts, and the identified CNVs were classified according to ACMG guidelines.

Método

Array-CGH

Resultados e Conclusões

Of 100 individuals (73 males and 27 females), abnormal CMA results were observed in 22 patients: 8 showed regions of homozygosity (LOH); 13 presented with CNVs only, and one individual had 2 CNVs besides LOHs. A total of fifteen CNVs were detected in 14 patients, being 7 duplications and 8 deletions. We identified two patients with known pathogenic CNVs: one Smith-Magenis syndrome (17p12p11.2 loss, 4.7Mb) and one 22q11.2 deletion syndrome-distal type I (22q11.21q11.22 loss, 2.06Mb). Furthermore, one patient presented with pathogenic losses at 16p13.11p12.3 (2.9Mb) and 18q23 (4.7Mb), two patients had CNVs classified as Likely Pathogenic (16p13.11 gain, 1.238Mb and 5p15.32p15.2 gain, 8.719Mb), and eight represented Variants of Unknown Significance. This study illustrates the potential of CMA analysis and the need for laboratory services to provide current scientific data in all case interpretations, as demonstrated here in our experience. Considering that we present a small sample of our routine, our findings are in line with the literature. The present work was able to show a reliable screening of the population with ASD, showing that the CMA together with the experience of the analysts, and the technical support of the laboratory, is a powerful combination to detect and interpret clinically relevant findings, leading to a better medical management and genetic counseling for affected people and their families.

Palavras Chave

array-CGH, Autism, CNV

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Nenhum conflito de interesses