A parent-of-origin effect in two families with retinoblastoma is associated with a distinct splice mutation in the RB1 gene.

ABSTRACT: We have identified a splice-site mutation (IVS6+1G-->T) in the RB1 gene, in two unrelated families with incomplete-penetrance retinoblastoma. Analysis of RNA from white blood cells showed that this mutation causes skipping of exon 6. Although this deletion results in a frameshift, most carriers of the mutation did not develop retinoblastoma. Interestingly, the relative abundance of the resultant nonsense messenger RNA varies between members of the same family and is either similar to or considerably lower than the transcript level of the normal allele. Moreover, variation of relative transcript levels is associated with both the sex of the parent that transmitted the mutant allele and phenotypic expression: All eight carriers with similar abundance of nonsense and normal transcript have re

SUBMITTER: Klutz M 

PROVIDER: S-EPMC384976 | biostudies-literature | 2002 Jul

REPOSITORIES: biostudies-literature