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Non-Invasive Prenatal Diagnosis of Retinoblastoma Inheritance by Combined Targeted Sequencing Strategies

Retinoblastoma, the most common childhood eye cancer, presents in two forms: heritable or sporadic. Heritable retinoblastoma is caused by a germline mutation in the RB1 gene. Early diagnosis of children at risk of inheriting an RB1 mutation is crucial to achieve optimal clinical outcome. Currently,...

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Autores principales: Gerrish, Amy, Bowns, Benjamin, Mashayamombe-Wolfgarten, Chipo, Young, Elizabeth, Court, Samantha, Bott, Joshua, McCalla, Maureen, Ramsden, Simon, Parks, Michael, Goudie, David, Carless, Sue, Clokie, Samuel, Cole, Trevor, Allen, Stephanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692133/
https://www.ncbi.nlm.nih.gov/pubmed/33143217
http://dx.doi.org/10.3390/jcm9113517
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author Gerrish, Amy
Bowns, Benjamin
Mashayamombe-Wolfgarten, Chipo
Young, Elizabeth
Court, Samantha
Bott, Joshua
McCalla, Maureen
Ramsden, Simon
Parks, Michael
Goudie, David
Carless, Sue
Clokie, Samuel
Cole, Trevor
Allen, Stephanie
author_facet Gerrish, Amy
Bowns, Benjamin
Mashayamombe-Wolfgarten, Chipo
Young, Elizabeth
Court, Samantha
Bott, Joshua
McCalla, Maureen
Ramsden, Simon
Parks, Michael
Goudie, David
Carless, Sue
Clokie, Samuel
Cole, Trevor
Allen, Stephanie
author_sort Gerrish, Amy
collection PubMed
description Retinoblastoma, the most common childhood eye cancer, presents in two forms: heritable or sporadic. Heritable retinoblastoma is caused by a germline mutation in the RB1 gene. Early diagnosis of children at risk of inheriting an RB1 mutation is crucial to achieve optimal clinical outcome. Currently, the majority of genetic testing is performed on newborns, which has multiple disadvantages for both families and the healthcare system. We have developed a non-invasive prenatal diagnosis (NIPD) service for retinoblastoma, available from 8 weeks’ gestation, which uses a combination of massively parallel sequencing (MPS) techniques, dependent on the inheritance model. Detection of paternal or suspected de novo RB1 variants is achieved through amplicon-based MPS. NIPD of a fetus at risk of maternal inheritance is performed using capture-based targeted sequencing and relative haplotype dosage analysis. In addition, we show proof of principle of how capture-based sequencing can be used for de novo variants unsuitable for amplicon-based testing. In total, we report the NIPD of 15 pregnancies, results of which show 100% concordance with all postnatal testing performed at the time of publication (n = 12) with remaining pregnancies ongoing. NIPD of retinoblastoma therefore offers a viable alternative to newborn genetic testing.
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spelling pubmed-76921332020-11-28 Non-Invasive Prenatal Diagnosis of Retinoblastoma Inheritance by Combined Targeted Sequencing Strategies Gerrish, Amy Bowns, Benjamin Mashayamombe-Wolfgarten, Chipo Young, Elizabeth Court, Samantha Bott, Joshua McCalla, Maureen Ramsden, Simon Parks, Michael Goudie, David Carless, Sue Clokie, Samuel Cole, Trevor Allen, Stephanie J Clin Med Article Retinoblastoma, the most common childhood eye cancer, presents in two forms: heritable or sporadic. Heritable retinoblastoma is caused by a germline mutation in the RB1 gene. Early diagnosis of children at risk of inheriting an RB1 mutation is crucial to achieve optimal clinical outcome. Currently, the majority of genetic testing is performed on newborns, which has multiple disadvantages for both families and the healthcare system. We have developed a non-invasive prenatal diagnosis (NIPD) service for retinoblastoma, available from 8 weeks’ gestation, which uses a combination of massively parallel sequencing (MPS) techniques, dependent on the inheritance model. Detection of paternal or suspected de novo RB1 variants is achieved through amplicon-based MPS. NIPD of a fetus at risk of maternal inheritance is performed using capture-based targeted sequencing and relative haplotype dosage analysis. In addition, we show proof of principle of how capture-based sequencing can be used for de novo variants unsuitable for amplicon-based testing. In total, we report the NIPD of 15 pregnancies, results of which show 100% concordance with all postnatal testing performed at the time of publication (n = 12) with remaining pregnancies ongoing. NIPD of retinoblastoma therefore offers a viable alternative to newborn genetic testing. MDPI 2020-10-30 /pmc/articles/PMC7692133/ /pubmed/33143217 http://dx.doi.org/10.3390/jcm9113517 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gerrish, Amy
Bowns, Benjamin
Mashayamombe-Wolfgarten, Chipo
Young, Elizabeth
Court, Samantha
Bott, Joshua
McCalla, Maureen
Ramsden, Simon
Parks, Michael
Goudie, David
Carless, Sue
Clokie, Samuel
Cole, Trevor
Allen, Stephanie
Non-Invasive Prenatal Diagnosis of Retinoblastoma Inheritance by Combined Targeted Sequencing Strategies
title Non-Invasive Prenatal Diagnosis of Retinoblastoma Inheritance by Combined Targeted Sequencing Strategies
title_full Non-Invasive Prenatal Diagnosis of Retinoblastoma Inheritance by Combined Targeted Sequencing Strategies
title_fullStr Non-Invasive Prenatal Diagnosis of Retinoblastoma Inheritance by Combined Targeted Sequencing Strategies
title_full_unstemmed Non-Invasive Prenatal Diagnosis of Retinoblastoma Inheritance by Combined Targeted Sequencing Strategies
title_short Non-Invasive Prenatal Diagnosis of Retinoblastoma Inheritance by Combined Targeted Sequencing Strategies
title_sort non-invasive prenatal diagnosis of retinoblastoma inheritance by combined targeted sequencing strategies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692133/
https://www.ncbi.nlm.nih.gov/pubmed/33143217
http://dx.doi.org/10.3390/jcm9113517
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