Abstract
BackgroundMutations in the transcription factor gene PAX6 have been shown to be the cause of the aniridia phenotype. The purpose of this study was to analyze patients with aniridia to uncover PAX6 gene mutations in south Indian population.MethodsTotal genomic DNA was isolated from peripheral blood of twenty-eight members of six clinically diagnosed aniridia families and 60 normal healthy controls. The coding exons of the human PAX6 gene were amplified by PCR and allele specific variations were detected by single strand conformation polymorphism (SSCP) followed by automated sequencing.ResultsThe sequencing results revealed novel PAX6 mutations in three patients with sporadic aniridia: c.715ins5, [c.1201delA; c.1239A>G] and c.901delA. Two previously reported nonsense mutations were also found: c.482C>A, c.830G>A. A neutral polymorphism was detected (IVS9-12C>T) at the boundary of intron 9 and exon 10. The two nonsense mutations found in the coding region of human PAX6 gene are reported for the first time in the south Indian population.ConclusionThe genetic analysis confirms that haploinsuffiency of the PAX6 gene causes the classic aniridia phenotype. Most of the point mutations detected in our study results in stop codons. Here we add three novel PAX6 gene mutations in south Indian population to the existing spectrum of mutations, which is not a well-studied ethnic group. Our study supports the hypothesis that a mutation in the PAX6 gene correlates with expression of aniridia.
Highlights
Mutations in the transcription factor gene PAX6 have been shown to be the cause of the aniridia phenotype
We used the single strand conformation polymorphism (SSCP) technique to search for mutations in exons 4–13 of the PAX6 gene (OMIM 106210) in probands with aniridia and normal controls
The fact that aniridia caused by intragenic mutation is phenotypically indistinguishable from aniridia caused by deletion of entire PAX6 gene makes it likely that the mutant alleles are null alleles [4,25]
Summary
Mutations in the transcription factor gene PAX6 have been shown to be the cause of the aniridia phenotype. Mutations in the transcription factor gene PAX6 cause blindness [2] through a spectrum of ocular manifestations among which aniridia and most probably foveal hypoplasia are the major signs [3,4,5]. Aniridia occurs due to decreased dosage of the PAX6 gene, which controls early events in the morphogenesis of the eye and brain [8,9]. It exists in both sporadic and familial forms
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