Abstract
Abstract: :
Purpose:Mutations in the transcription factor gene PAX6 have been shown to be the cause of aniridia phenotype. The purpose of this study is to investigate genotype/phenotype correlations in aniridia patients with PAX6 mutations in the south Indian population. Methods: Eight clinically well–characterized sporadic aniridia individuals with their unaffected family members (27) and normal healthy controls (80) were studied. Total genomic DNA was isolated from peripheral blood of aniridia patients and controls. The coding exons of the human PAX6 gene were amplified by PCR. Nucleotide changes were detected by single strand conformation polymorphism analysis (SSCP) followed by automated sequencing. Results:The sequencing results revealed novel PAX6 mutations in four patients with sporadic aniridia: c.1180insA, c.715ins5, c.1201delA, and c.901delA. Three nonsense mutations: c.1080 C>T, c.482C>A, c.830G>A. were also reported here for the first time in South Indian population, even though these mutations were reported in other populations. A neutral polymorphism was detected (IVS9–12C>T) at the boundary of intron 9 and exon 10. Conclusion:Most genetic analysis indicates that haploinsuffiency of the PAX6 gene causes the classic aniridia phenotype. Most mutations detected in aniridia patients results in premature termination of translation from the mutant allele. We add four novel PAX6 gene mutations to the existing spectrum of mutations in Indian population. Our study supports the hypothesis that mutations in the PAX6 gene cause the pathological aniridia phenotype.