Spectrum of RB1 mutations identified in 403 retinoblastoma patients

J Med Genet. 2014 Mar;51(3):208-14. doi: 10.1136/jmedgenet-2013-101821. Epub 2013 Nov 13.


Background: Retinoblastoma (RB) is a malignant, childhood tumour of the developing retina that occurs with an estimated frequency of 1 in 20 000. Identification of oncogenic mutations in the RB1 gene aids in the clinical management of families with a heritable predisposition to RB. Here we present the spectrum of genetic and epigenetic changes identified in 194 tumours and 209 blood samples, from 403 unrelated RB patients.

Methods: Mutation screening was carried out across all 27 RB1 exons and their associated splice sites. Small coding sequence changes were detected using fluorescent conformation analysis followed by sequencing. Large exonic deletions were detected by quantitative fluorescent PCR. Methylation specific PCR of the RB1 promoter was performed to detect epigenetic alterations. Polymorphism analysis was used to determine loss of heterozygosity in tumour samples.

Results: 95% of the expected mutations were identified in the tumour samples, with 16 samples exhibiting only one mutation, while two samples had no detectable RB1 mutation. 96% of bilateral/familial RB blood samples and 9.5% of unilateral sporadic blood samples, yielded mutations. 111 were novel mutations.

Conclusions: The full range of screening techniques is required to achieve a high screening sensitivity in RB patients.

Keywords: Genetic Screening/Counselling.

MeSH terms

  • Child, Preschool
  • Cohort Studies
  • DNA Mutational Analysis
  • Genes, Retinoblastoma / genetics*
  • Humans
  • Infant
  • Mutation / genetics*
  • Retinal Neoplasms / epidemiology
  • Retinal Neoplasms / genetics*
  • Retinoblastoma / epidemiology
  • Retinoblastoma / genetics*