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Evaluating the Clinical Utility of Genome Sequencing for Cytogenetically Balanced Chromosomal Abnormalities in Prenatal Diagnosis

Balanced chromosomal abnormalities (BCAs) are changes in the localization or orientation of a chromosomal segment without visible gain or loss of genetic material. BCAs occur at a frequency of 1 in 500 newborns and are associated with an increased risk of multiple congenital anomalies and/or neurode...

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Autores principales: Yu, Mullin Ho Chung, Chau, Jeffrey Fong Ting, Au, Sandy Leung Kuen, Lo, Hei Man, Yeung, Kit San, Fung, Jasmine Lee Fong, Mak, Christopher Chun Yu, Chung, Claudia Ching Yan, Chan, Kelvin Yuen Kwong, Chung, Brian Hon Yin, Kan, Anita Sik Yau
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873444/
https://www.ncbi.nlm.nih.gov/pubmed/33584815
http://dx.doi.org/10.3389/fgene.2020.620162
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author Yu, Mullin Ho Chung
Chau, Jeffrey Fong Ting
Au, Sandy Leung Kuen
Lo, Hei Man
Yeung, Kit San
Fung, Jasmine Lee Fong
Mak, Christopher Chun Yu
Chung, Claudia Ching Yan
Chan, Kelvin Yuen Kwong
Chung, Brian Hon Yin
Kan, Anita Sik Yau
author_facet Yu, Mullin Ho Chung
Chau, Jeffrey Fong Ting
Au, Sandy Leung Kuen
Lo, Hei Man
Yeung, Kit San
Fung, Jasmine Lee Fong
Mak, Christopher Chun Yu
Chung, Claudia Ching Yan
Chan, Kelvin Yuen Kwong
Chung, Brian Hon Yin
Kan, Anita Sik Yau
author_sort Yu, Mullin Ho Chung
collection PubMed
description Balanced chromosomal abnormalities (BCAs) are changes in the localization or orientation of a chromosomal segment without visible gain or loss of genetic material. BCAs occur at a frequency of 1 in 500 newborns and are associated with an increased risk of multiple congenital anomalies and/or neurodevelopmental disorders, especially if it is a de novo mutation. In this pilot project, we used short read genome sequencing (GS) to retrospectively re-sequence ten prenatal subjects with de novo BCAs and compared the performance of GS with the original karyotyping. GS characterized all BCAs found by conventional karyotyping with the added benefit of precise sub-band delineation. By identifying BCA breakpoints at the nucleotide level using GS, we found disruption of OMIM genes in three cases and identified cryptic gain/loss at the breakpoints in two cases. Of these five cases, four cases reached a definitive genetic diagnosis while the other one case had a BCA interpreted as unknown clinical significance. The additional information gained from GS can change the interpretation of the BCAs and has the potential to improve the genetic counseling and perinatal management by providing a more specific genetic diagnosis. This demonstrates the added clinical utility of using GS for the diagnosis of BCAs.
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spelling pubmed-78734442021-02-11 Evaluating the Clinical Utility of Genome Sequencing for Cytogenetically Balanced Chromosomal Abnormalities in Prenatal Diagnosis Yu, Mullin Ho Chung Chau, Jeffrey Fong Ting Au, Sandy Leung Kuen Lo, Hei Man Yeung, Kit San Fung, Jasmine Lee Fong Mak, Christopher Chun Yu Chung, Claudia Ching Yan Chan, Kelvin Yuen Kwong Chung, Brian Hon Yin Kan, Anita Sik Yau Front Genet Genetics Balanced chromosomal abnormalities (BCAs) are changes in the localization or orientation of a chromosomal segment without visible gain or loss of genetic material. BCAs occur at a frequency of 1 in 500 newborns and are associated with an increased risk of multiple congenital anomalies and/or neurodevelopmental disorders, especially if it is a de novo mutation. In this pilot project, we used short read genome sequencing (GS) to retrospectively re-sequence ten prenatal subjects with de novo BCAs and compared the performance of GS with the original karyotyping. GS characterized all BCAs found by conventional karyotyping with the added benefit of precise sub-band delineation. By identifying BCA breakpoints at the nucleotide level using GS, we found disruption of OMIM genes in three cases and identified cryptic gain/loss at the breakpoints in two cases. Of these five cases, four cases reached a definitive genetic diagnosis while the other one case had a BCA interpreted as unknown clinical significance. The additional information gained from GS can change the interpretation of the BCAs and has the potential to improve the genetic counseling and perinatal management by providing a more specific genetic diagnosis. This demonstrates the added clinical utility of using GS for the diagnosis of BCAs. Frontiers Media S.A. 2021-01-27 /pmc/articles/PMC7873444/ /pubmed/33584815 http://dx.doi.org/10.3389/fgene.2020.620162 Text en Copyright © 2021 Yu, Chau, Au, Lo, Yeung, Fung, Mak, Chung, Chan, Chung and Kan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Yu, Mullin Ho Chung
Chau, Jeffrey Fong Ting
Au, Sandy Leung Kuen
Lo, Hei Man
Yeung, Kit San
Fung, Jasmine Lee Fong
Mak, Christopher Chun Yu
Chung, Claudia Ching Yan
Chan, Kelvin Yuen Kwong
Chung, Brian Hon Yin
Kan, Anita Sik Yau
Evaluating the Clinical Utility of Genome Sequencing for Cytogenetically Balanced Chromosomal Abnormalities in Prenatal Diagnosis
title Evaluating the Clinical Utility of Genome Sequencing for Cytogenetically Balanced Chromosomal Abnormalities in Prenatal Diagnosis
title_full Evaluating the Clinical Utility of Genome Sequencing for Cytogenetically Balanced Chromosomal Abnormalities in Prenatal Diagnosis
title_fullStr Evaluating the Clinical Utility of Genome Sequencing for Cytogenetically Balanced Chromosomal Abnormalities in Prenatal Diagnosis
title_full_unstemmed Evaluating the Clinical Utility of Genome Sequencing for Cytogenetically Balanced Chromosomal Abnormalities in Prenatal Diagnosis
title_short Evaluating the Clinical Utility of Genome Sequencing for Cytogenetically Balanced Chromosomal Abnormalities in Prenatal Diagnosis
title_sort evaluating the clinical utility of genome sequencing for cytogenetically balanced chromosomal abnormalities in prenatal diagnosis
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873444/
https://www.ncbi.nlm.nih.gov/pubmed/33584815
http://dx.doi.org/10.3389/fgene.2020.620162
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