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Abeyratne L.R.,Hillingdon Hospital | Kingston J.E.,Great Ormond Street Hospital | Onadim Z.,Retinoblastoma Genetic Screening Unit | Dubrey S.W.,Hillingdon Hospital
BMJ Case Reports | Year: 2013

Heritable retinoblastoma is associated with a germline mutation in the tumour suppressor gene RBI . The Rb protein ( pRb) arises from the RB1 gene, which was the first demonstrated cancer susceptibility gene in humans.Second primary malignancies are recognised complications of retinoblastoma. Furthermore, pRb is implicated in valve remodelling in calcific aortic valve disease. 2 3 We report a family with hereditary retinoblastoma and associated secondary primary malignancies. There are two interesting aspects to this family. The first is the concept of 'cancer susceptibility genes'; the RBI gene being the first reported in humans. A further feature of note is that two family members also have bicuspid aortic valves. We discuss a potential association between the gene defect responsible for retinoblastoma (with its associated propensity for further malignancies) and accelerated deterioration of the bicuspid aortic valve in the proband carrying this gene defect. Copyright 2013 BMJ Publishing Group. All rights reserved. Source


Price E.A.,Retinoblastoma Genetic Screening Unit | Price K.,Retinoblastoma Genetic Screening Unit | Kolkiewicz K.,Retinoblastoma Genetic Screening Unit | Hack S.,Retinoblastoma Genetic Screening Unit | And 5 more authors.
Journal of Medical Genetics | Year: 2014

Background: Retinoblastoma (RB) is a malignant, childhood tumour of the developing retina that occurs with an estimated frequency of 1 in 20 000. Identification of oncogenic mutations in the RB1 gene aids in the clinical management of families with a heritable predisposition to RB. Here we present the spectrum of genetic and epigenetic changes identified in 194 tumours and 209 blood samples, from 403 unrelated RB patients. Methods: Mutation screening was carried out across all 27 RB1 exons and their associated splice sites. Small coding sequence changes were detected using fluorescent conformation analysis followed by sequencing. Large exonic deletions were detected by quantitative fluorescent PCR. Methylation specific PCR of the RB1 promoter was performed to detect epigenetic alterations. Polymorphism analysis was used to determine loss of heterozygosity in tumour samples. Results: 95% of the expected mutations were identified in the tumour samples, with 16 samples exhibiting only one mutation, while two samples had no detectable RB1 mutation. 96% of bilateral/familial RB blood samples and 9.5% of unilateral sporadic blood samples, yielded mutations. 111 were novel mutations. Conclusions: The full range of screening techniques is required to achieve a high screening sensitivity in RB patients. Source

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