Frequency and nature of germline Rb-1 gene mutations in a series of patients with sporadic unilateral retinoblastoma

Eur J Cancer. 1999 Dec;35(13):1824-7. doi: 10.1016/s0959-8049(99)00171-9.


Constitutional Rb-1 gene mutations were studied in a series of 17 families with isolated unilateral retinoblastoma patients. Peripheral blood lymphocytes were analysed by karyotyping, Southern blot hybridisation, and 'exon by exon' sequencing. Mutations were detected in 4 (24%) of the investigated probands. All mutations were identified by sequencing. No alteration was detected by Southern blotting or karyotyping. In one of our cases with a R358 stop codon mutation, retinoblastoma was unilateral at the time of diagnosis, but a tumour of the second eye was diagnosed after 35 months of follow-up. After exclusion of this case, the frequency of constitutional mutations in our series was 19% (3 of 16 cases). Alterations in our cases without involvement of the second eye included G-->A substitution in the promoter region 198 bp upstream of the initiating methionine codon; G-->C transversion in the splice donor site at position +1 leading to exon 6 skipping and a 137 bp in-frame deletion, starting 3 bp from the 5' end of exon 15 to 27 bp from the 3' end of exon 16. All alterations were germline de novo abnormalities.

MeSH terms

  • Blotting, Southern
  • Genes, Retinoblastoma / genetics*
  • Germ-Line Mutation / genetics*
  • Humans
  • Karyotyping
  • Retinal Neoplasms / genetics*
  • Retinoblastoma / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction / methods