Cargando…

Prenatal Chromosomal Microarray Analysis: Does Increased Resolution Equal Increased Yield?

Chromosomal microarray analysis (CMA) is considered a first-tier test for patients with developmental disabilities and congenital anomalies and is also routinely applied in prenatal diagnosis. The current consensus size cut-off for reporting copy number variants (CNVs) in the prenatal setting ranges...

Descripción completa

Detalles Bibliográficos
Autores principales: Mitrakos, Anastasios, Kosma, Konstantina, Makrythanasis, Periklis, Tzetis, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454647/
https://www.ncbi.nlm.nih.gov/pubmed/37628571
http://dx.doi.org/10.3390/genes14081519
_version_ 1785096245968109568
author Mitrakos, Anastasios
Kosma, Konstantina
Makrythanasis, Periklis
Tzetis, Maria
author_facet Mitrakos, Anastasios
Kosma, Konstantina
Makrythanasis, Periklis
Tzetis, Maria
author_sort Mitrakos, Anastasios
collection PubMed
description Chromosomal microarray analysis (CMA) is considered a first-tier test for patients with developmental disabilities and congenital anomalies and is also routinely applied in prenatal diagnosis. The current consensus size cut-off for reporting copy number variants (CNVs) in the prenatal setting ranges from 200 Kb to 400 Kb, with the intention of minimizing the impact of variants of uncertain significance (VUS). Very limited data are currently available on the application of higher resolution platforms prenatally. The aim of this study is to investigate the feasibility and impact of applying high-resolution CMA in the prenatal setting. To that end, we report on the outcomes of applying CMA with a size cut-off of 20 Kb in 250 prenatal samples and discuss the findings and diagnostic yield and also provide follow-up for cases with variants of uncertain significance. Overall, 19.6% (49) showed one or more chromosomal abnormalities, with the findings classified as Pathogenic (P) or Likely Pathogenic (LP) in 15.6% and as VUS in 4%. When excluding the cases with known familial aberrations, the diagnostic yield was 12%. The smallest aberration detected was a 32 Kb duplication of the 16p11.2 region. In conclusion, this study demonstrates that prenatal diagnosis with a high-resolution aCGH platform can reliably detect smaller CNVs that are often associated with neurodevelopmental phenotypes while providing an increased diagnostic yield, regardless of the indication for testing, with only a marginal increase in the VUS incidence. Thus, it can be an important tool in the prenatal setting.
format Online
Article
Text
id pubmed-10454647
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-104546472023-08-26 Prenatal Chromosomal Microarray Analysis: Does Increased Resolution Equal Increased Yield? Mitrakos, Anastasios Kosma, Konstantina Makrythanasis, Periklis Tzetis, Maria Genes (Basel) Article Chromosomal microarray analysis (CMA) is considered a first-tier test for patients with developmental disabilities and congenital anomalies and is also routinely applied in prenatal diagnosis. The current consensus size cut-off for reporting copy number variants (CNVs) in the prenatal setting ranges from 200 Kb to 400 Kb, with the intention of minimizing the impact of variants of uncertain significance (VUS). Very limited data are currently available on the application of higher resolution platforms prenatally. The aim of this study is to investigate the feasibility and impact of applying high-resolution CMA in the prenatal setting. To that end, we report on the outcomes of applying CMA with a size cut-off of 20 Kb in 250 prenatal samples and discuss the findings and diagnostic yield and also provide follow-up for cases with variants of uncertain significance. Overall, 19.6% (49) showed one or more chromosomal abnormalities, with the findings classified as Pathogenic (P) or Likely Pathogenic (LP) in 15.6% and as VUS in 4%. When excluding the cases with known familial aberrations, the diagnostic yield was 12%. The smallest aberration detected was a 32 Kb duplication of the 16p11.2 region. In conclusion, this study demonstrates that prenatal diagnosis with a high-resolution aCGH platform can reliably detect smaller CNVs that are often associated with neurodevelopmental phenotypes while providing an increased diagnostic yield, regardless of the indication for testing, with only a marginal increase in the VUS incidence. Thus, it can be an important tool in the prenatal setting. MDPI 2023-07-25 /pmc/articles/PMC10454647/ /pubmed/37628571 http://dx.doi.org/10.3390/genes14081519 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mitrakos, Anastasios
Kosma, Konstantina
Makrythanasis, Periklis
Tzetis, Maria
Prenatal Chromosomal Microarray Analysis: Does Increased Resolution Equal Increased Yield?
title Prenatal Chromosomal Microarray Analysis: Does Increased Resolution Equal Increased Yield?
title_full Prenatal Chromosomal Microarray Analysis: Does Increased Resolution Equal Increased Yield?
title_fullStr Prenatal Chromosomal Microarray Analysis: Does Increased Resolution Equal Increased Yield?
title_full_unstemmed Prenatal Chromosomal Microarray Analysis: Does Increased Resolution Equal Increased Yield?
title_short Prenatal Chromosomal Microarray Analysis: Does Increased Resolution Equal Increased Yield?
title_sort prenatal chromosomal microarray analysis: does increased resolution equal increased yield?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454647/
https://www.ncbi.nlm.nih.gov/pubmed/37628571
http://dx.doi.org/10.3390/genes14081519
work_keys_str_mv AT mitrakosanastasios prenatalchromosomalmicroarrayanalysisdoesincreasedresolutionequalincreasedyield
AT kosmakonstantina prenatalchromosomalmicroarrayanalysisdoesincreasedresolutionequalincreasedyield
AT makrythanasisperiklis prenatalchromosomalmicroarrayanalysisdoesincreasedresolutionequalincreasedyield
AT tzetismaria prenatalchromosomalmicroarrayanalysisdoesincreasedresolutionequalincreasedyield