Mutational and Clinical Spectrum of the PAX6 Gene in Bulgarian Patients with Aniridia

Abstract

The PAX6 gene has highly conservative structure and developmentally essential function and is expressed in structurally different organs and systems. Haploinsufficiency of the PAX6 gene product leads to aniridia and aniridia-like phenotypes. A total of 9 patients and 115 controls were examined with the use of a variety of molecular-genetics methods (SNP array, Sanger sequencing, NGS, WES) and in collaboration with different clinicians. Two pathogenic CNVs, three potentially pathogenic variants and two nonsynonymous SNVs in the PAX6 gene were identified: two out of the three potentially pathogenic variants have not been previously reported. The heterogeneous nature of aniridia and the variable spectrum of the PAX6 mutations were confirmed by our study. Approximately 75% of the registered cases in the Bulgarian population were studied and five disease-related variants were discovered. The small number of polymorphic variants in the controls supports the highly conserved role and nature of the PAX6 and its product.