Background: Retinoblastoma, the intraocular malignancy most common in children,occurs in both familial and sporadic (bilateral or unilateral). Hereditary predisposition is caused by a germ-line mutation while non-hereditary is due to two somatic mutations in a retinal cell. This work was carried out in order to analyse genetically, the high number of families with some affected member and to go deep into the molecular mechanisms responsible of this pathology.
Patients and method: 59 families with one or more affected members were analysed. Cytogenetics and with polymorphic markers studies were carried out and a search for mutations was performed in DNA from white cells and from available tumoral tissue.
Results: In four of the 5 familial cases, the responsible mutation was established,the same as in 9 of the 13 bilateral sporadic. In the 7% of the unilateral sporadic cases, mutation was found in leucocytary DNA. Lost of heterozygosity as a second mutational event was mainly due to mitotic recombination.
Conclusions: Among the mutations of our series, a higher frequency of punctual mutations,responsible of the first mutational event, was observed at constitutional level. Lost of heterozygosity was the mechanism observed in the majority of the tumours.