Sequencing of RB1 Gene and In Silico Analysis in Western Algerian Population Affected by Retinablastoma

Abstract

Retinoblastoma (RB) is an intraocular malignant tumour which occurs in children during the first months of life, with an incidence of 1 in 15,000 live births. Antioncogene RB1 located on chromosome 13q14.2, is at the origin of this pathology. For retinoblastoma development, two allele mutations of this gene are required. The aim of this study firstly, was to identify mutations that affect the RB1 gene in constitutional level, to detect early subject at risk or asymptomatic carriers and secondly to contribute on the understanding of the molecular pathogenesis. The study concerned 61 patients with retinoblastoma in Western Algeria. DNA from blood was used for amplification and gene sequencing. The results were completed by in-silico analysis using bio-informatic methods to know the mutation impact on the pRB1 protein function. Amplification and sequencing results gave nineteen different variations bases, including eight exonic changes: three missense mutations and five nonsense mutations located in exons 1,7,8,12,18,19,20 and 23. There are an important number of mutations located in twelve RB1 gene introns. These mutations were identified in germinal level for children with no family history of the disease. In conclusion, this study reported two new RB1 mutations in exons 1 and 7 among the eight identified. The mutations described in sporadic forms of retinoblastoma are transmissible forms in 13.11% of cases in our studied population. This study would improve role of genetic testing for management and family screening.