Molecular Screening of PAX2 Gene Polymorphism in Primary Vesicoureteral Reflux Patients in Taif Governorate, KSA.

Abstract

Background and Objective: Primary Nonsyndromic Vesicoureteral Reflux (PVUR) is a widespread genetic malformation and considered a prevalent Congenital Abnormality of the Kidney and Urinary Tract (CAKUT). Mutations in the PAX2 gene have been associated with abnormalities in the kidney extending from CAKUT to oncogenic processes. The present study analyzes the PAX2 polymorphisms and their association with primary VUR in Saudi children patients from the Taif governorate. Materials and Methods: Fifteen children with primary VUR were identified and screened for gene mutations in the PAX2 gene by direct sequencing method of purified Polymerase Chain Reaction (PCR) products of all exons to elucidate the correlation between PAX2 gene and VUR. Results: Seven new variants have been defined. Three polymorphic missense variants in homozygous genotype form were found in intron 8 and detected in eight patients, One missense mutation was found in exon 10 in the site of transactivation domain and detected in ten patients and in-silico analysis predicted it as a pathogenic one, Three mutations were found in exon 11 and detected in all patients as a compound homozygous. Conclusion: PAX2is important for normal kidney development and mutations in the gene possibly lead to disturbance in the protein structure and could be non-functional thus mutations in PAX2 may be one of the causes of PVUR in Saudi Arabia. Further investigation is necessary to understand the aetiology of disease and maybe other genes implicated in VUR.