Non-Invasive Prenatal Diagnosis of Retinoblastoma Inheritance by Combined Targeted Sequencing Strategies
Open Access
- 30 October 2020
- journal article
- research article
- Published by MDPI AG in Journal of Clinical Medicine
- Vol. 9 (11), 3517
- https://doi.org/10.3390/jcm9113517
Abstract
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.This publication has 29 references indexed in Scilit:
- Noninvasive prenatal testing for autosomal recessive conditions by maternal plasma sequencing in a case of congenital deafnessGenetics in Medicine, 2014
- Noninvasive Prenatal Diagnosis of Monogenic Diseases by Targeted Massively Parallel Sequencing of Maternal Plasma: Application to β-ThalassemiaClinical Chemistry, 2012
- Maternal Plasma DNA Sequencing Reveals the Genome-Wide Genetic and Mutational Profile of the FetusScience Translational Medicine, 2010
- Quantitative Analysis of Fetal DNA in Maternal Plasma and Serum: Implications for Noninvasive Prenatal DiagnosisAmerican Journal of Human Genetics, 1998
- Parental origin of germ-line and somatic mutations in the retinoblastoma geneHuman Genetics, 1994
- Mechanisms of loss of heterozygosity in retinoblastomaCytogenetic and Genome Research, 1992
- Somatic and Germinal Mutations of Tumor-Suppressor Genes in the Development of CancerJournal of Radiation Research, 1991
- Parental origin of mutations of the retinoblastoma geneNature, 1989
- Types, rates, origin and expressivity of chromosome mutations involving 13q14 in retinoblastoma patientsHuman Genetics, 1988
- Mutation and Cancer: Statistical Study of RetinoblastomaProceedings of the National Academy of Sciences of the United States of America, 1971