Molecular Diagnosis of Genetic Diseases of the Kidney: Primer for Pediatric Nephrologists

In an age of competing medical priorities, why should healthcare professionals who are already overloaded with information develop core competencies in genetics and genomics? [1] The genomic architecture of kidney disease has fascinated developmental biologists and human geneticists for over four decades. Seminal discoveries of note include the discovery of genes implicated in autosomal dominant/recessive polycystic kidney disease, nephronophthisis, and nephrotic syndrome. Uncovering disease-causing genes has helped refine our pathogenetic understanding of many renal diseases, and in many cases, it has directly translated into a concrete improvement of patient care. The recent emergence of next-generation sequencing strategies has dramatically sped up the discovery process and constitutes the cornerstone towards the realization of personalized medicine. This chapter summarizes basic genomic/genetic concepts before delving into recent advances that are pertinent to the practice of contemporary pediatric nephrologists. From laboratory methods to the interpretation of genetic variants, we present every topic within a clinical framework enriched with many examples from the pediatric nephrology literature. The major benefits of genomics to the day-to-day practice of busy clinicians are: it will expedite diagnosis, clarify prognosis, and guide therapeutic choices. Our overarching goals for this chapter were two-fold: to first convince clinicians “already overloaded with information” that learning about genomics is a worthwhile investment that will pay dividends in the short-term, while providing an accessible port of entry into this complex field.