Genetic screening in patients with Retinoblastoma in Israel

Abstract Retinoblastoma (Rb) is a childhood tumor (~1 in 20,000 live births) developing in the retina due to mutations in the RB1 gene. Identification of the oncogenic mutations in the RB1 gene is important for the clinical management and for genetic counseling to families with a child or a parent affected with the tumor. Here we present our experience in detecting the pathogenic mutations in blood samples, from 150 unrelated Rb patients and highlight the relevant counseling issues. Mutation screening in the RB1 gene was based on Sanger sequencing, mosaicism of recurrent CpG transition mutations was detected by allele specific PCR and multiplex ligation dependent probe amplification for detecting of large deletions/duplications. The overall detection rate of mutations in our cohort was 55 % (82/150). In the familial cases it was 100 % (17/17), in bilateral and unilateral-multifocal sporadic cases 91 % (50/55), and in the unilateral sporadic cases 19 % (15/78). Nonsense mutations and small deletions or insertions that results in transcripts with premature termination codons that are subject to nonsense mediated decay were the most frequent, detected in 50/82 (61 %) of the patients. The rest were large deletions detected in 14/82 (17 %), splice site mutations detected in 11/82 (13 %), missense mutations in four patients and mutations in the promoter sequence in three patients. Mutation mosaicism ranging from 10 to 30 % was detected by allele specific P...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research