Detection of germline mutations in argentine retinoblastoma patients: low and full penetrance retinoblastoma caused by the same germline truncating mutation

J Biochem Mol Biol. 2004 Mar 31;37(2):246-53. doi: 10.5483/bmbrep.2004.37.2.246.


Constitutional RB1 gene mutations were studied in a series of 21 families with unilateral and bilateral retinoblastoma patients. Peripheral blood lymphocytes were analyzed by "exon by exon" PCR-heteroduplex and sequencing. Mutations were identified in 6 (29%) of the patients. One mutation corresponded to an intronic polymorphism in g.174351T > A. The other five mutations resulted C to T exonic transitions, four were CGA sequences (g.65386, g.150037 in two patients, and g.162237), creating stop codons and presumably truncated proteins. The fifth one was new and resulted in alanine to valine substitution (g.73774). Two patients had the same the germline truncated mutation (g.150037C > T), one with a familial bilateral early onset retinoblastoma and one with a sporadic unilateral late onset retinoblastoma. The later type has not been previously described. This finding is discussed in the genotype/phenotype correlation context. Additionally, a single nucleotide change was found in six studied samples, where a C to T homozygous transversion was identified in intron 26 (IVS26 + 28). It is worthy the non concordance of the nucleotide with the published sequence. This analysis proved to be a useful method for the detection of mutations in the RB1 gene, and contributed to the adequate genetic counseling to patients and relatives.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Amino Acid Substitution
  • Argentina
  • Base Pair Mismatch
  • Codon, Nonsense
  • Codon, Terminator
  • DNA Mutational Analysis
  • Female
  • Germ-Line Mutation*
  • Heteroduplex Analysis
  • Humans
  • Introns
  • Male
  • Pedigree
  • Penetrance*
  • Polymorphism, Genetic
  • Retinoblastoma / chemistry
  • Retinoblastoma / genetics*
  • Retinoblastoma / physiopathology
  • Valine / metabolism


  • Codon, Nonsense
  • Codon, Terminator
  • Valine