Genotype-phenotype correlation analysis in retinoblastoma patients from India.

BACKGROUND: Genetic analysis has a beneficial impact on retinoblastoma management enabling definite risk assessment. However, information regarding genotype-phenotype correlation in retinoblastoma is limited. AIM: To analyze the retinoblastoma susceptibility gene for mutations in retinoblastoma patients and correlate the genotypes the phenotypes. METHODOLOGY: Eleven retinoblastoma patients, who underwent molecular genetic studies were classified into high, moderate or low disease severity groups based on phenotype. RESULTS: Seven patients had high disease severity and four moderate disease severity. Eleven truncating mutations were detected; six were in the N-terminus region of the retinoblastoma protein and two in the A/B pocket (p=0.03). CONCLUSIONS: No significant association between mutation type and disease severity could be established in the present study. However a positive correlation between location of the mutations in certain domains of the retinoblastoma protein and disease severity was observed. To the best of our knowledge this is the first genotype-phenotype correlation study in retinoblastoma patients from India.

RPE65 gene: multiplex PCR and mutation screening in patients from India with retinal degenerative diseases.

We used multiplex PCR follwed by sequencing to screen for mutations in the 14 exons of the RPE65 gene in early-childhood-onset autosomal recessive retinitis pigmentosa (arRP) and Leber's congenital amaurosis (LCA) patients. The RPE65 protein is believed to play an important role in the metabolism of vitamin A in the visual cycle and mutations identified in the gene could have implications for vitamin A-based therapeutic intervention. We were able to identify a homozygous mutation (AAT --> AAG) in exon 9 in an arRP patient and a heterozygous missense transversion (AAT --> AAG) also in exon 9 of an LCA patient. We also identified a polymorphism in exon 10 (GAG --> GAA) in an arRP as well as an LCA patient. Mutation screening would be greatly facilitated by multiplex PCR which could cut down costs, labour and time involved. The nucleotide changes observed in this study could be de novo. Though a larger study has been undertaken, from the preliminary results it appears that in India the RPE65 gene seems to be less involved in causation of LCA.