Report of a novel mutation in Rb1 gene from an Iranian retinoblastoma patient and its effect on splicing pattern of mRNA

Mutations in RB1 gene may lead to retinoblastoma which is the most common solid intraocular tumor in under-six year old children. To date, a wide spectrum of the mutations has been reported in the splicing of RB1 which either affect splicing sequences or splicing regulatory elements. This report introduces a new mutation in RB1and its influence on the splicing of mRNA. Case report: In the present survey, mutation analysis was done in an Iranian patient with sporadic unilateral retinoblastoma using direct sequencing and MLPA. Also, RB1 gene splicing pattern was analyzed by RT-PCR method. As a result, a same-sense nucleotide change (g.70 320C>T) was found near the 5' end of exon 12. This alteration disrupts the consensus sequence of an exonic splicing enhancer and changes the binding site of SC-35 protein. Structural analysis of cDNA in this patient showed the disruption of normal splicing pattern and the skipping of exon 12 from the RB1 transcript. Based on these findings, it may be reasonable to conclude that the above nucleotide change could be a pathogenic mutation. Also, for the first time we report an evidence for the presence of an exonic splicing enhancer in the exon 12 of the RB1 gene.