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

Abstract

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.

Advances in Target Therapy Research in Osteosarcoma

“…Indeed, mutations in this gene have been commonly associated with hereditary osteosarcoma. The RB1 protein plays a crucial role in cell cycle control, and its dysfunction can lead to uncontrolled cell proliferation, a common trait in tumors [6]. For example, Li-Fraumeni syndrome is linked to mutations in the TP53 gene, which is involved in Disclaimer/Publisher's Note: The statements, opinions, and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s).…”

Genetic Component of Retinoblastoma in Bukavu, Democratic Republic of Congo

“…In light of the results of numerous studies conducted worldwide, which continue to develop new mutation variants of the RB1 gene [8][9][10][11][12][13][14], advances in research into the mutational spectrum of the RB1 gene, for both diagnostic and therapeutic purposes, are revolutionizing the management of RB. Commonly described mutations are nonsense (56%), frameshift (12%), splice site changes (12%) and missense (12%).…”