Novel variants in the PAX6 gene related to isolated aniridia

Aniridia, which is a rare congenital defect of the eye, consists of iris hypoplasia or aplasia, and additional ocular abnormalities. It is most commonly caused by autosomal dominant PAX6 gene mutations. However, in about 30% of cases, it is associated with chromosomal rearrangements in the 11p13 region. The aim of this study was to identify the potential PAX6 gene variants, which could cause the isolated aniridia. Eight patients with isolated aniridia were included in this study. MLPA analysis allowed in the past to exclude large structural rearrangements of the PAX6 and adjacent genes like WT1. Blood samples were collected from the patients (and their families in familial cases) and genomic DNA was extracted from peripheral blood leukocytes and buccal cells. The amplification of the 11 exons of the PAX6 gene was performed. Bidirectional Sanger Sequencing was conducted for the identification of the potentially pathogenic variants, and for the segregation analysis of the identified variant in the family. The results were analyzed with the use of CodonCode Aligner software. In three patients, aniridia was sporadic, whereas in another five cases, the eye defect was familial. The potentially pathogenic variants in the PAX6 gene were found in 6 out of 8 patients with aniridia. We identified four known (c.781C > T, c.607C > T, and c.949C > T twice), and two novel variants (c.258_265del and c.495_496insG). Point mutations in the PAX6 gene are the most frequent cause of aniridia. The investigation of the genetic background of the disease is essential for patients to evaluate recurrence risk in the offspring.