Genetic kidney diseases.
Knowledge of the primary cause of a disease is essential for elucidation of its mechanisms, and for adequate classification, prognosis, and treatment. Recently, the causes of many kidney diseases have been shown to be single-gene defects-eg, steroid-resistant nephrotic syndrome, which is caused by podocin mutations in about 25% of children and nearly 15% of adults with the disease. Knowledge of a disease-causing mutation in a single-gene disorder represents one of the most robust diagnostic examples of personalised medicine because the mutation conveys an almost 100% risk of developing the disease by a defined age. Whereas single-gene diseases are rare disorders, polygenic risk alleles arise in common adult-onset diseases. In this Review, I will discuss prominent renal single-gene kidney disorders, and polygenic risk alleles of common disorders. I delineate how emerging techniques of total exome capture and large-scale sequencing will assist molecular genetic diagnosis, prognosis, and specific treatment, and lead to an improved elucidation of disease mechanisms, thus enabling development of new targeted drugs.
Hildebrandt
Friedhelm
F
Howard Hughes Medical Institute and Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA. fhilde@umich.edu
D006801:Humans; D007668:Kidney / Q000002:abnormalities; D007674:Kidney Diseases / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D014551:Urinary Tract / Q000002:abnormalities
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