Retinoblastoma (RB) is a childhood cancer developing in the retina due to RB1 pathologic variant. Herein we are evaluating the oncogenic mutations in the RB1 gene and the inheritance patterns of RB in the Jordanian patients. In this prospective study, the peripheral blood of 50 retinoblastoma patients was collected, genomic DNA was extracted, mutations were identified using Quantitative multiplex PCR (QM-PCR), Allele-specific PCR, Next Generation Sequencing analysis, and Sanger sequencing. In this cohort of 50 patients, 20(40%) patients had unilateral RB and 30(60%) were males. Overall, 36(72%) patients had germline disease, 17(47%) of whom had the same RB1 pathologic variant detected in one of the parents (inherited disease). In the bilateral group, all (100%) patients had germline disease; 13(43%) of them had inherited mutation. In the unilateral group, 6(30%) had germline disease, 4(20%) of them had inherited mutation. Nonsense mutation generating a stop codon and producing a truncated non-functional protein was the most frequent detected type of mutations (n = 15/36, 42%). Only one (2%) of the patients had mosaic mutation, and of the 17 inherited cases, 16(94%) had an unaffected carrier parent. In conclusion, in addition to all bilateral RB patients in our cohort, 30% of unilateral cases showed germline mutation. Almost half (47%) of germline cases had inherited disease from affected (6%) parent or unaffected carrier (94%). Therefore molecular screening is critical for the genetic counseling regarding the risk for inherited RB in both unilateral and bilateral cases including those with no family history.
Germline Mutation RB1 gene Retinoblastoma
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We want to thank The Impact Genetics Lab Inc. (Ontario, Canada), mainly Prof. B, Gallie (Laboratory Director and RB Medical Director), F. Jewett (Managing Director), and H. Racher, PHD (Scientific and Laboratory Director) for providing us with mutational analysis for RB1 gene in our patients. Also we thank Mr. Raed Marashdeh, and Mr. Ahmad Qawas from King Hussein Cancer Center for solving all issues related to logistics.
This research was supported by an intra-mural grant from the Research Council, King Hussein Cancer Center (Grant No. 13KHCC25) (Amman, Jordan).
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
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