Identification of the first several nephrotic syndrome and focal segmental glomerulosclerosis (FSGS) genes has had a significant impact on the understanding of glomerular function and disease. However, It is clear that the known genes account for only a fraction of these diseases. Here our goal is further elucidation of the genetic basis of FSGS, using a database of over 2500 individuals assembled over the past eleven years. Specifically, we will perform mutational analysis of known FSGS genes in families with FSGS and in patients with sporadic FSGS. We will continue our ongoing ascertainment of families with FSGS as well as sporadic adult and pediatric cases. Mutational analysis of these known FSGS genes will further inform our understanding of the spectrum of mutations, inform genotype/phenotype relationships, provide further information regarding structure and function, and help clarify the utility of genetic testing. We will also aim to Identify new FSGS genes. Through genome-wide scans, we have identified several genetic regions that appear to harbor as yet unidentified FSGS genes. We will analyze genes within these disease-associated regions in order to identify disease-associated variation. We will continue to perform additional genome-wide scans in new, genetically informative families as they are ascertained. We will test the hypothesis that rare DNA sequence variants in critical podocyte/glomerulus genes contribute to the etiology of FSGS. We will resequence candidate genes in 300 FSGS cases and 300 controls and determine if rare deleterious variants in these genes are more common in cases. We will replicate positive results in independent sample sets. FSGS is a significant and growing cause of chronic kidney disease and kidney failure. FSGS is also a common consequence of a variety of primary conditions. These studies will help understand the underlying causes of this disease.

Public Health Relevance

The identification of new focal segmental glomerulosclerosis (FSGS) genes and further genetic characterization of known FSGS genes will have significant implications for understanding, and ultimately, treating, common forms of renal failure and renal failure progression. In the more immediate future, identification and characterization of FSGS gene defects will have implications for the development of diagnostic tools.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Cellular and Molecular Biology of the Kidney Study Section (CMBK)
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Rasooly, Rebekah S
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Beth Israel Deaconess Medical Center
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Feng, Di; Steinke, Julia M; Krishnan, Ramaswamy et al. (2016) Functional Validation of an Alpha-Actinin-4 Mutation as a Potential Cause of an Aggressive Presentation of Adolescent Focal Segmental Glomerulosclerosis: Implications for Genetic Testing. PLoS One 11:e0167467
Ruchi, Rupam; Genovese, Giulio; Lee, Jessica et al. (2015) Copy Number Variation at the APOL1 Locus. PLoS One 10:e0125410
Pollak, Martin R (2015) Idiopathic pediatric chronic kidney disease: can genomic technology crack the case? J Clin Invest 125:1799-800
Sampson, Matthew G; Pollak, Martin R (2015) Opportunities and Challenges of Genotyping Patients With Nephrotic Syndrome in the Genomic Era. Semin Nephrol 35:212-21
Barua, Moumita; Shieh, Eric; Schlondorff, Johannes et al. (2014) Exome sequencing and in vitro studies identified podocalyxin as a candidate gene for focal and segmental glomerulosclerosis. Kidney Int 85:124-33
Brown, Elizabeth J; Pollak, Martin R; Barua, Moumita (2014) Genetic testing for nephrotic syndrome and FSGS in the era of next-generation sequencing. Kidney Int 85:1030-8
Pollak, Martin R (2014) Familial FSGS. Adv Chronic Kidney Dis 21:422-5
Gbadegesin, Rasheed A; Hall, Gentzon; Adeyemo, Adebowale et al. (2014) Mutations in the gene that encodes the F-actin binding protein anillin cause FSGS. J Am Soc Nephrol 25:1991-2002
Barua, Moumita; Stellacci, Emilia; Stella, Lorenzo et al. (2014) Mutations in PAX2 associate with adult-onset FSGS. J Am Soc Nephrol 25:1942-53
Grgic, Ivica; Hofmeister, Andreas F; Genovese, Giulio et al. (2014) Discovery of new glomerular disease-relevant genes by translational profiling of podocytes in vivo. Kidney Int 86:1116-29

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