Identification of a mutation in exon 27 of the RB1 gene associated with incomplete penetrance retinoblastoma.

Retinoblastoma (Rb) is initiated by germline mutations in the RB1 gene. Up to date, no mutation was identified in exons 26 and 27. We have identified a 2 bp frameshift insertion in exon 27 of the RB1 gene (RBg.

Patterns of missplicing caused by RB1 gene mutations in patients with retinoblastoma and association with phenotypic expression.

We have analyzed RNA from retinoblastoma patients and unaffected carriers with various RB1 gene mutations to determine the patterns of missplicing and associations with phenotypic expression. Most sequence alterations in or in the neighborhood of conserved splice signals that we tested resulted in simple exon skipping (15 mutations) or intron inclusion (new acceptor AG-sites, four mutations) as expected. Two mutations resulted in skipping of a neighboring exon (exon 11), a complex pattern indicating competition for correct lariat formation.