Purpose: To study phenotype-genotype correlation in patients with hereditary retinoma, a benign tumor wich presents either as an old retinal scar or as a mass resembling the post irradiation regression pattern of retinoblastoma.
Methods: We selected bilaterally affected patients with retinoma in one eye and either retinoma or retinoblastoma in the other eye. All patients underwent full ophthalmic examination. After obtaining informed consent, DNA was extracted from peripheral blood leucocytes and the RB1 gene was screened by DHPLC and direct sequencing of the promoter and all the exons.
Results: Twenty-one patients with available DNA were included in the study. We identified a germline mutation in 16 of the 21 patients. Out of the 16 patients with identified mutations, 14 cases were familial, from 8 families, and 2 cases were sporadic. Thus, we had 10 index cases in total. The 10 identified mutations were located in exons 1, 10,11,13,14 and 19 to 23. Four of the identified mutations were not previously reported, these are g.64407delT, g.153236A>T, g.156743delTCTG and g.162078delA. Truncating mutations were found in 12 out the 16 cases, and missense mutations in the remaining 4 cases. There was no correlation between the type of mutation and the number of tumor foci per eye (retinoblastoma or retinomas). Inter and intrafamilial significantly heterogeneous expressivity was observed.
Conclusions: The present study suggests that the type of inherited mutation is not the determinant factor for the development of retinomas. We postulate that genetic or epigenetic modifier factors might be involved, as well as the nature of the second, non-inherited mutation.