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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,...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7692133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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