Genomic Approaches for Monogenic Kidney Diseases: A Comparative Review of Diagnostic Methods and Precision Medicine Implications

Abstract

Chronic kidney disease is a long-term condition with significant implications for quality of life and health care costs. To uncover the etiology in selected cases suspected of monogenicity, a genomic approach can be employed. There are multiple technologies available, but there is currently no consensus on the most effective diagnostic approach. This review provides a comparison of currently available diagnostic methods in terms of diagnostic yield. However, the heterogeneity of patient cohort inclusion criteria limits direct comparisons. Our review identified three studies which compared a targeted gene panel and whole-exome sequencing for the same patient population. However, the results are inconclusive due to the different sizes and specificity of the targeted panels employed. The contribution of a whole-genome sequencing approach is highly debated. It is noteworthy that a large number of data are generated by these sequencing technologies. This allows for rapid analysis of coding and non-coding regions. However, the interpretation of variants is a significant burden, and the reporting of incidental findings is still challenging. Therefore, the identification of the most efficient technology is pivotal but still controversial. To conclude, an objective comparison of the three methods for the same population could overcome the limits of these studies’ heterogeneity and highlight the weaknesses and the strengths of individual approaches.

Keywords

• genetic testing
• CKD
• diagnostic yield
• review
• diagnostic approach