Five novel RB1 gene mutations and genotype–phenotype correlations in Chinese children with retinoblastoma

PURPOSE: To identify the spectrum of RB1 gene mutations in 114 Chinese patients with retinoblastoma. METHODS: Genomic DNA was extracted from the peripheral blood of 114 Rb patients. Polymerase chain reactions (PCRs) followed by direct Sanger sequencing were used to screen for mutations in the RB1 gene, which contains 26 exons with flanking intronic sequences, except exon 15. Clinical data, including gender, age at diagnosis, laterality of ocular lesions, and associated symptoms, were recorded and compared. RESULTS: We identified five novel mutations in the RB1 gene. Twenty-five other mutations found in this study have been previously reported. A higher rate of RB1 mutations, with 47.3% of mutations among bilaterally affected patients vs. 6.8% within unilaterally affected patients, was also observed (p < 0.0001). Bilaterally affected patients were diagnosed earlier when compared to unilaterally affected patients (11 ± 7 months versus 20 ± 14 months, p = 0.0002). Furthermore, nonsense mutations were abundant (n = 14), followed by frameshift mutations (n = 8), splicing site mutations (n = 5), while missense mutations were few (n = 3). CONCLUSIONS: We found five novel mutations in RB1 genes, which expands the mutational spectrum of the gene. Children with bilateral Rb exhibited higher mutation rates and were diagnosed earlier than those with unilateral Rb. These findings will inform clinical diagnosis and genetic therapeutic targeting in Rb patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10792-022-02341-2.