1Molecular and Diagnostics Personalized Therapeutic Unit University of Hail School of Medicine, Hail, Kingdom of Saudi Arabia
2University of Hail, College of Applied Medical Sciences, Hail, Kingdom of Saudi Arabia
3Chronic Disease Program, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
4Functional Endoproteolysis Laboratory Clinical Research Institute of Montreal, Montreal, Quebec, Canada
*Corresponding e-mail: a.nuglozeh@uoh.edu.sa
Online published on 23 November, 2018.
Chronic kidney disease and renal failure are major health concerns in Saudi Arabia, especially in the Hail region. These diseases are commonly coupled with hypertension and hypercholesterolemia. Genetic factors strongly contribute to them. This study was undertaken in an effort to identify genetic variations that might contribute to renal failure in the Hail population.
We performed Whole Exome Sequencing (WES) on genomic DNA of four unrelated Hail patients afflicted by renal failure. Exonic variations located in genes known to be implicated the disease were selected and validated by Sanger sequencing.
In all four patients, we identified a c. C803T transition in exon 2 of the angiotensinogen gene (AGT), causing an M268T amino acid substitution in the protein. All four patients were homozygous for T268 allele.
AGT is implicated in blood pressure regulation; it contributes to normal kidney function. The M268T AGT mutation has been known to be associated with hypertension and kidney disease. Whether or not it is a determinant of the kidney failure of our patients could be established if family studies show segregation of the mutant allele with the disease. This study illustrates how WES can be used to identify candidate genetic variations for inherited kidney diseases.
Whole-exome sequencing, Renal failure, Angiotensinogen, Saudi Arabia
