AUTHOR=Bierzynska Agnieszka , Soderquest Katrina , Koziell Ania TITLE=Genes and Podocytes – New Insights into Mechanisms of Podocytopathy JOURNAL=Frontiers in Endocrinology VOLUME=5 YEAR=2015 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2014.00226 DOI=10.3389/fendo.2014.00226 ISSN=1664-2392 ABSTRACT=

After decades of primarily morphological study, positional cloning of the NPHS1 gene was the landmark event that established aberrant podocyte genetics as a pivotal cause of malfunction of the glomerular filter. This ended any uncertainty whether genetic mutation plays a significant role in hereditary nephrotic syndromes (NS) and confirmed podocytes as critical players in regulating glomerular protein filtration. Although subsequent sequencing of candidate genes chosen on the basis of podocyte biology had less success, unbiased analysis of genetically informative kindreds and syndromic disease has led to further gene discovery. However, the 45 genes currently associated with human NS explain not more than 20–30% of hereditary and only 10–20% of sporadic cases. It is becoming increasingly clear both from genetic analysis and phenotypic data – including occasional response to immunosuppressive agents and post-transplant disease recurrence in Mendelian disease – that monogenic inheritance of abnormalities in podocyte-specific genes disrupting filter function is only part of the story. Recent advances in genetic screening technology combined with increasingly robust bioinformatics are set to allow identification and characterization of novel disease causing variants and more importantly, disease modifying genes. Emerging data also support a significant but incompletely characterized immunoregulatory component.