RB1 Gene Mutations and Genetic Spectrum in Retinoblastoma Cases

The aim of the study was to investigate the frequency and types of mutations on the RB1 gene at the familial, clinical, and ethnic levels which are known to have an important role in the genetics of retinoblastoma in Turkish population. RB1 gene mutation analysis was performed in 219 people (122 probands, 14 family members with retinoblastoma and 83 clinically healthy family members) in total. All 27 exons and close intronic regions of the RB1 gene were sequenced for small deletions and insertions using both the Sanger sequencing or NGS methods, and also the large deletions and duplications were investigated by both the Multiplex Ligation Probe Amplification (MLPA) analysis and the Copy Number Variation (CNV) algorithm. The general RB1 gene mutation frequency of the patients with retinoblastoma was 41.9%. The bilateral retinoblastoma rate was 34.5% in our study population. It was striking that approximately 51.5% of our patients were diagnosed 12 months earlier, and de novo mutation occurred in 90.4% of the patients. Small genetic rearrangement mutations were detected in 78.9% of patients and Large Genetic Rearrangement (LGR) was detected in 21.1% of patients. There was a relationship between the eye color of the RB patients and RB1 mutations. As a conclusion, the familial, clinical and ethnical level of the RB1 gene mutations which are known to have a significant role in genetics of retinoblastoma were investigated, and different RB1 mutations, 10 of which are novel, have been identified on the RB1 gene sequence.