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

Amy Gerrish (Lead / Corresponding author), Benjamin Bowns, Chipo Mashayamombe-Wolfgarten, Elizabeth Young, Samantha Court, Joshua Bott, Maureen McCalla, Simon Ramsden, Michael Parks, David Goudie, Sue Carless, Samuel Clokie, Trevor Cole, Stephanie Allen

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12 Citations (Scopus)
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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.

Original languageEnglish
Article number3517
Number of pages12
JournalJournal of Clinical Medicine
Issue number11
Publication statusPublished - 30 Oct 2020


  • retinoblastoma
  • prenatal diagnosis
  • non-invasive
  • cell-free DNA


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