A T to C mutation in the polypyrimidine tract of the exon 9 splicing site of the RB1 gene responsible for low penetrance hereditary retinoblastoma.

Inactivation of both alleles of the retinoblastoma susceptibility gene (RB1), localised on chromosome band 13q14, is the crucial event for the development of retinoblastoma, a malignant tumour that originates from embryonal retinal cells. 2 Germinal mutation of one allele leads to a predisposition to retinoblastoma. Tumour development is initiated by inactivation of the second allele. In most families, the tumour predisposition segregates as an autosomal dominant trait with high (90%) penetrance and affected subjects usually develop bilateral multifocal tumours. Rare instances of familial retinoblastoma with low penetrance and variable expressivity have been described. In such families, patients develop retinoblastoma later than classical familial cases, there is a high rate of unilateral cases, and phenotypically normal obligate carriers are observed.