Clinical and genetic characteristics of retinoblastoma patients in a single center with four novel RB1 variants.

Abstract

To assess the clinical and genetic characteristics of children diagnosed with retinoblastoma (RB) at Gazi University Faculty of Medicine's Department of Pediatric Oncology. All cases diagnosed with RB and received treatment and follow-up in the Ophthalmology and Pediatric Oncology Department, October 2016 to May 2021 were evaluated retrospectively. The RB1 gene was analyzed by next-generation sequencing (NGS) technique in DNAs obtained from peripheral blood samples of the patients. This study included 53 cases with 67 RB-affected eyes during the study period. The mean age was 24.6 (median: 18.5, range: 3-151)mo. There were 15 (22.3%) Group D eyes and 39 (58.2%) Group E eyes. The RB1 gene was sequenced by the NGS method in 19 patients. Heterozygous RB1:NM_000321.3: c.54_76del (p.Glu19AlafsTer4) variant was detected in a 15-month-old female with bilateral RB. Heterozygous RB1:NM_000321.3: c.1814+3A>T variant was detected in a 5.5-month-old male with bilateral RB. The intronic RB1:NM_000321.3: c.1332+4A>G variant was detected in patient 14, a 13-month-old male with unilateral RB. The RB1:NM_000321.3: c.575_576del (p.Lys192SerfsTer10) variant was found in an 18-month-old female with an allele frequency of 37%. These variants have not been reported in the literature and mutation databases. Four novel variants are described and one of them is found in two different patients. This data is crucial for assessing prognosis. It serves as a guide for estimating the long-term risk of secondary malignancy as well as the short-term risk of developing additional malignancies in the same eye and the other eye.