Chapter 22 - Inherited Kidney Disorders in the Age of Genomics

Abstract

The importance of genetics for nephrology is underlined by the fact that more than 200 genes have been associated with inherited renal disease. Information about the genotypes of patients with kidney disease is key to providing an early and accurate diagnosis and determining prognosis. In addition, genetics influences patient management and allows for the development of targeted therapeutics. After briefly discussing major developments in the genetics field, this review focuses on the development of next-generation sequencing (NGS) technology that can be used to analyze numerous genes or even whole genomes in a single experiment. This technology allowed for the rapid identification of novel disease genes for a variety of recessive and dominant renal disorders, varying from congenital anomalies of the kidney and urinary tract to atypical hemolytic uremic syndrome and nephronophthisis to adult-onset focal segmental glomerulosclerosis. This review discusses how to interpret NGS data, summarizes NGS discoveries in the kidney field, highlights challenges with respect to technology and variant interpretation, and underlines the importance of NGS usage in the nephrology clinic. We discuss how sequencing of all or a selection of coding DNA is progressing toward whole-genome analysis, and we touch on how NGS has opened an era of personalized medicine that includes drug screening, gene therapy, and tissue regeneration therapy.