[Distinct Rb gene point mutations in families showing low penetrance of hereditary retinoblastoma]

To investigate the possible cause and molecular mechanism of low penetrance in hereditary retinoblastoma kindred.

The DNAs from tumor or blood of affected and unaffected individuals in hereditary retinoblastoma families showing low penetrance were screened by SSCP analysis and further characterized by direct DNA sequencing.

Eight from fifteen families showing low penetrance retinoblastoma were identified to have distinct Rb gene point mutations including Arg661-Trp661 in five families, aberrant splicing in two families and a G-T mutation at ATF binding site of Rb gene promoter in one family.

The distribution of cases with low penetrance of retinoblastoma is not completely random. The low penetrance in the families described here was associated with several distinct Rb gene point mutations which did not result in complete disruption of the gene product,and the reduced penetrance of retinoblastoma is probably the result of a residual function of these alleles in retinoblastoma precursor cells.