The Promise of Exome Sequencing for the Differential Diagnosis of Late-Onset End-Stage Renal Disease in Turkish Cypriots

TL;DR

This study explores how exome sequencing can help diagnose late-onset end-stage renal disease in Turkish Cypriots, highlighting the need for more population-based research.

Contribution

The study re-analyzes exome sequencing data to identify potential genetic causes of ESRD in a specific population.

Findings

Exome sequencing revealed multiple genes and variants potentially linked to ESRD in Turkish Cypriots.

Common variants across patients limit population-based conclusions about ESRD etiology.

The study emphasizes the need for larger cohort studies and a whole genome database for better diagnosis.

Abstract

End-stage renal disease (ESRD) is a pathophysiological condition that requires radical solutions for treatment. Although ESRD is a worldwide health problem, the incidence of the disease is relatively high in the Mediterranean island of Cyprus. Moreover, the etiology of the disease largely remains poorly understood. Overlapping diseases such as diabetes mellitus may pose a challenge during the differential diagnosis of ESRD. Hence, molecular diagnosis could be powerful in terms of ESRD diagnosis. Nevertheless, the genetic isolation of Cyprus and the complexity of the disease necessitate more comprehensive, population-based approaches. In the current study, exome sequencing (ES) data obtained from 24 Turkish Cypriot patients with ESRD were re-analyzed. Variants were filtered according to the allele frequencies in population databases and the renal anomalies-related gene list. Variants were then prioritized according to the guidelines of the American College of Medical Genetics. The re-analysis underscored that different genes and their variants could explain the molecular mechanisms of the disease. However, numerous variants were found to be prevalent in all patients, limiting the ability to reach a population-based conclusion about the aetiology of ESRD in Cyprus. Although ES could be useful for the molecular diagnosis of ESRD, further population-based cohort studies and a whole genome database with data from healthy participants are still needed.