Detection of mutations in argentine retinoblastoma patients by segregation of polymorphisms, exon analysis and cytogenetic test.

The aim of this study was to detect chromosomal and molecular abnormalities in 16 Argentine families with retinoblastoma (RB). Chromosomes were analyzed by G-banding, DNA from leukocytes and tumors was studied by segregation of polymorphisms within RB gene (RB1) and the DNA from chorionic villus by sequencing. The karyotype of an Rb236 bilateral patient with dismorphic signs revealed a deletion in 13q13-21. Polymorphism and exon analyses showed a deletion in the 3' end of RB1 in an Rb72 patient. The mutant RB1 allele, detected by loss of heterozygosity (LOH) in the tumor, was identified in 14 out of 18 tumors. The analysis of chorionic villus revealed a mutation, a C-to-T transition in exon 18. Molecular and cytogenetic analyses in families with RB offer valuable information on how to assess the risk of tumor development.

Clinical, cytogenetic, and molecular testing of Argentine patients with retinoblastoma.

PURPOSE: The purpose of this study is to determine the clinical, chromosomal, and molecular characteristics of Argentine patients with unilateral and bilateral retinoblastoma. STUDY DESIGN: Eighty-six patients belonging to 82 families were studied; 59% of them were examined during the first year of life. Leukocoria was the most common reason for consultation. Other presenting signs were strabismus and glaucoma. Enucleation of the affected eye was performed in 85% of the cases and the complication rate was 13%. RESULTS: An appropriate therapy allowed the survival of 84 of the 86 patients. Two children with malformations and growth retardation had an abnormal karyotype with a deletion in 13q14. Segregation analysis of polymorphic sites within the retinoblastoma gene and the parental origin of the allele lost in the tumor were analyzed in 30 of the 82 families. Five mutant alleles transmitted through the germline and six de novo germline mutant alleles were identified in 12 patients with hereditary retinoblastoma. Most de novo germline mutant alleles were paternally derived. Molecular analysis of nonhereditary retinoblastoma showed loss of heterozygosity in three of eight cases. From these, two maternal alleles and one paternal allele were lost, thus not indicating a significant difference in the parental origin for the lost allele. CONCLUSIONS: These data are useful for deoxyribonucleic acid diagnosis of susceptibility to retinoblastoma in relatives of hereditary patients, even if mutations have not been identified.