Prenatal diagnosis: the clinical usefulness of array comparative genomic hybridization

Marta Freitas; Joel Pinto; Carla Ramalho; Sofia Dória

doi:10.1016/j.pbj.0000000000000013

Prenatal diagnosis: the clinical usefulness of array comparative genomic hybridization

Porto Biomed J. 2018 Jul 3;3(2):e13. doi: 10.1016/j.pbj.0000000000000013. eCollection 2018 Oct.

Authors

Marta Freitas^{1

2}, Joel Pinto^{2

3}, Carla Ramalho^{3

4

5}, Sofia Dória^{2

3}

Affiliations

¹ Faculty of Medicine, University of Porto, Portugal.
² Genetics Unit, Department of Pathology, Faculty of Medicine.
³ I3S - Instituto de Investigação e Inovação em Saúde, University of Porto.
⁴ Department of Gynecology and Obstetrics, Centro Hospitalar de São João, EPE.
⁵ Department of Gynecology, Obstetrics and Pediatrics, Faculty of Medicine, University of Porto, Porto, Portugal.

Abstract

Background: Array comparative genomic hybridization (aCGH) has been replacing karyotype in neurodevelopment diseases or intellectual disability cases. Regarding prenatal diagnosis (PND) karyotyping is still the criterion standard technique; nevertheless, the application of aCGH in this field has been increasing dramatically and some groups recommended it as the first-tier prenatal genetic test in cases of fetal ultrasound abnormalities. Despite aCGH greater resolution, the detection of variants of unknown significance (VOUS) is not desirable, so it's need some reflexion before generalized application on PND.

Objective: The aim of this study was to analyze the prevalence and type of copy number variants (CNVs) detected in the 55 PND samples collected from pregnancies with indication to perform aCGH.

Methods: aCGH was performed using Agilent 4 × 180K microarrays and results were analyzed using CytoGenomics software.

Results and conclusion: Eight (14.5%) cases had pathogenic or likely pathogenic CNVs. VOUS were found in 21.8% of the cases, but this frequency could be minimized if only large CNVs above 1 million base pairs that are outside the clinically curated targeted regions were considered.

Keywords: array comparative genomic hybridization; copy number variation; karyotype; prenatal diagnosis; variants of unknown significance.