Genetic screening in Iranian patients with retinoblastoma

Abstract

Purpose The most common intraocular tumor in childhood, retinoblastoma, is largely associated with mutations in the RB1 gene. In the most comprehensive RB1 screening in Iran, we evaluated the RB1 mutations in 106 patients with retinoblastoma, including 73 bilateral (heritable) and 33 unilateral (sporadic) cases. Patients and methods Mutations were identified using amplification refractory mutation system (ARMS) PCR and direct sequencing of the 27 coding exons of RB1 and multiplex ligation-dependent probe amplification (MLPA). Results and ConclusionWe found 33 (31%) and 64 (60%) patients with sporadic unilateral and bilateral retinoblastoma, respectively as well as 9 (8.5%) cases with hereditary bilateral retinoblastoma. In total, we identified 52 causative RB1 mutations in 106 patients (global mutation rate of 49%). Of the 52 patients, 48 (92%) had sporadic and familial bilateral and 4 (8%) had sporadic unilateral RB. Therefore, the detection rate of RB1 mutations was 66% (48/73) and 12% (4/33) in bilateral and unilateral cases, respectively. Mutations were classified as nonsense in 31 (60%), missense in 1 (2%), large deletion in 11 (21%), small deletion in the 7 novel (15%) and splice site mutation in 2 (4%) patients with RB. Of 31 nonsense mutations, 23 (74%) occurred in the 11 Arginine codons of the RB1. Seven mutations (13%) were novel, and 45 (87%) had been previously reported. Thirty-three mutations were single-base substitutions leading to 31 nonsense amino acid changes and 2 splice site mutations in introns 12 and 16 of RB1. The altered 3D model structures of the RB1 novel mutant proteins are also predicted in this study.

Molecular Genetic Analysis ofRB1gene among Sudanese children with Retinoblastoma

“…Despite the incomplete records, Leukocoria seems to be the most common presenting sign at presentation (13 patients). This finding is consistent with the result reported by K Shahraki et al in Iran that the Leukocoria represent the major complaints of RB patients (60). Regarding laterality of the disease, our results were slightly different than that in the literatures where unilateral tumors occupied 77.4% and bilateral tumors 19.4% compared to ~ 60% unilateral and 40% bilateral worldwide (2,6,7,24).…”

The Concordance of Paternal and Maternal Retinoblastoma-1 Gene Mutation Pattern with Clinical Manifestation and Disease Staging in Patients Suffering from Retinoblastoma

“…They also demonstrated 38 different causative RB1 mutations among patients, with an RB1 mutation detection rate of 65.8%. In this study, we detected more than 19 different mutations among RB1 patients (16). Ghassemi and colleagues showed that the most common presenting stage of RB1-carrying patients at IAC therapy was the D group, reaching up to 75%, followed by the E group and C group at the first visit.…”

Secondary Malignancies in Adulthood and after Retinoblastoma Treatment in Childhood

“…The main criteria in determining the result of a mutation is its location in the 3D structure. The altered 3D model structures of the Rb1 novel mutant proteins are also available today [6,7]. Improvements in survival, from a 3-year survival rate of 76% in the 1970s to a 5-year survival rate of 97% since the mid-1990s, are due to advances in treatment [2,8,9].…”