Purpose: To study phenotype-genotype correlations in 65 retinoblastoma patients, who were seen between March 2004 and January 2006 and to report undescribed retinoblastoma 1 (RB1) mutations identified in ten additional patients in whom mutations were detected before 2004.
Methods: Complete ophthalmic examinations were performed in all patients and their parents. DNA was extracted from peripheral blood leukocytes, and the RB1 gene was screened by denaturing high-performance liquid chromatography and direct sequencing of the promoter and all the exons.
Results: Seven cases were familial, 30 were sporadic bilateral, and 28 were sporadic unilateral. Screening of the RB1 gene resulted in the identification of four mutations in the familial cases (57%), 22 in the sporadic bilateral cases (73%), and three in the sporadic unilateral cases (10.7%). Twenty-two mutations, were single-base substitutions (76%). Of these mutations, 68% were of the nonsense type (15 cases). Ten patients with bilateral retinoblastoma in whom ten mutations were detected in a non-systematic approach between 1995 and 1998 were added to our recent series. In total, ten novel mutations were identified, including four single base substitutions, four small deletions and two small duplications. These are g.39445G>A, g.41924A>G, g.56851A>G, g.156795T>G, g.41983delT, g.44699_44706delAGCAGTTC, g.73788_73789delAA, g.78253delA, g.2157dupC, and g.2179_2183dupGGACC. Two patients had dysmorphic features associated with 13q14 large deletions.
Conclusions: The detection rates of 73% in the sporadic bilateral cases and of 10.7% in the sporadic unilateral cases in our series are in accordance with recently published literature. Our pattern of mutations confirms the predominantly gene-inactivating mutations, i.e. single-base non-sense mutations and splice site mutations.