RB1 germline mutation spectrum and clinical features in patients with unilateral retinoblastomas

Ophthalmic Genet. 2021 Oct;42(5):593-599. doi: 10.1080/13816810.2021.1946703. Epub 2021 Jun 30.


Background: Retinoblastoma is the most common intraocular cancer in children in which above 90% of bilateral cases and 10-25% of unilateral cases have germline RB1 mutations. We summarized the spectrum of RB1 germline mutations and the clinical manifestations of unilateral retinoblastomas to guide clinical treatments.Methods: Two hundred and sixty-three unrelated patients with unilateral retinoblastoma and their parents were included between February 2014 and August 2020. Next-generation sequencing and Sanger sequencing analysis of the core promoter region and exons 1-27 including flanking intronic regions of the RB1 gene were performed. If a germline mutation was identified in a retinoblastoma patient, the parental blood sample was requested to test for the identified mutation.Results: RB1 germline mutations were identified in 39/263 (14.8%) unilateral retinoblastoma patients and 11 (28.2%) had a missense mutation, 10 (25.6%) had nonsense mutations, 2 (5.1%) had frameshifts, 1 (2.6%) had synonymous mutation, and 7 (17.9%) had a large deletion, 2 (5.1%) had splice site mutations, 6 (15.4%) had variant of uncertain significance. Moreover, 27 (69.2%) of 39 patients identified RB1 mutations were predicted to have pathogenic mutation. The median age at diagnosis of patients with identified RB1 pathogenic mutations was 16.9 months and the patients with the wild-type allele was 21.1 months (P = .323).Conclusion: The rate of germline RB1 mutations is 14.8% in our cohort of unilateral retinoblastomas. The high incidence of germline mutations indicates that genetic testing and counseling for families of unilateral retinoblastoma patients would be beneficial.

Keywords: Children; genetic testing; germline mutation; next-generation sequencing; retinoblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics
  • Child
  • Child, Preschool
  • China / epidemiology
  • DNA Mutational Analysis
  • Exons
  • Female
  • Genes, Retinoblastoma
  • Genetic Testing
  • Germ-Line Mutation*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Infant, Newborn
  • Introns
  • Male
  • Retinal Neoplasms / epidemiology
  • Retinal Neoplasms / genetics*
  • Retinal Neoplasms / pathology
  • Retinoblastoma / epidemiology
  • Retinoblastoma / genetics*
  • Retinoblastoma / pathology
  • Retinoblastoma Binding Proteins / genetics*
  • Ubiquitin-Protein Ligases / genetics*


  • RB1 protein, human
  • Retinoblastoma Binding Proteins
  • Ubiquitin-Protein Ligases