PAX6 gene mutations and genotype-phenotype correlations in sporadic cases of aniridia from India

Abstract

In order to understand the underlying molecular genetic defect causing aniridia in India, eight probands from sporadic cases were screened for all 14 exons of the PAX6 gene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). Direct sequencing of the SSCP variants revealed a nonsense mutation (R317X) in the eleventh exon leading to a premature termination of the PAX6 protein in the proline-serine-threonine (PST)-rich domain in two probands. Another proband exhibited an intronic polymorphism (IVS 9-12 C-T). The mutation resulted in loss of function of the PAX6 protein along with variable phenotypic manifestations in the probands. This is the first report describing a PAX6 gene mutation in aniridia cases from India and highlights the variable expressivity in phenotypes due to haploinsufficiency.