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Chapter 3 - Idiopathic and Hereditary Proteinuric Glomerular Diseases

from Section 2 - Glomerular Diseases

Published online by Cambridge University Press:  10 August 2023

By
Danica Galešić Ljubanović  and
Parker Wilson
Edited by
Helen Liapis
Helen Liapis
Affiliation:
Ludwig Maximilian University, Nephrology Center, Munich, Adjunct Professor and Washington University St Louis, Department of Pathology and Immunology, Retired Professor
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Summary

This chapter discusses exclusively the pathology and molecular genetics of non-immune-complex mediated glomerular diseases characterized predominantly by proteinuria due to defects in the podocyte filtration barrier. The clinical classification of steroid sensitive and steroid resistant nephrotic syndrome and histopathology patterns are discussed in parallel or interchangeably. More than 50 podocyte gene mutations associated with nephrotic syndrome have been identified. These have changed the management and general outlook of childhood nephrotic glomerular diseases. A detail account of the genetics of nephrotic syndrome associated glomerular pathologies is provided in the section “Molecular Pathology.”

Keywords

Podocytopathynephrotic syndrome (NS)steroid sensitive NS (SSNS)steroid resistant NS (SRNS)minimal change disease (MCD)focal segmental glomerulosclerosis (FSGS)collapsing glomerulopathy (CGP)diffuse mesangial sclerosis (DMS)congenital nephrotic syndrome (CNS)nephrin (NPHS1)podocin (NPHS2)
Type
Chapter
Information
Pediatric Nephropathology & Childhood Kidney Tumors , pp. 27 - 55
Publisher: Cambridge University Press
Print publication year: 2023

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References

Chang-Chien, C., Chuang, G. T., Tsai, I. J., Chiang, B. L., Yang, Y. H.. A large retrospective review of persistent proteinuria in children. J Formos Med Assoc 2018;117:711–19.CrossRefGoogle ScholarPubMed
Jang, K. M., Cho, M. H Clinical approach to children with proteinuria. Child Kidney Dis 2017;21:53–60.CrossRefGoogle Scholar
Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int Suppl 2012;2:139–74.Google Scholar
Barisoni, L., Schnaper, H. W., Kopp, J. B.. A proposed taxonomy for the podocytopathies: A reassessment of the primary nephrotic diseases. Clin J Am Soc Nephrol 2007;2:529–42.CrossRefGoogle ScholarPubMed
Stone, H. K., Parameswaran, S., Eapen, A. A., Chen, X., Harley, J. B., Devarajan, P., et al. Comprehensive review of steroid-sensitive nephrotic syndrome genetic risk loci and transcriptional regulation as a possible mechanistic link to disease risk. Kidney Int Rep 2020;16;6:187–95.Google Scholar
Farquhar, M. G., Vernier, R. L., Good, R. A.. An electron microscope study of the glomerulus in nephrosis, glomerulonephritis, and lupus erythematosus. J Exp Med 1957;106: 649–60.CrossRefGoogle ScholarPubMed
Maas, R. J., Deegens, J. K., Wetzels, J. F.. Permeability factors in idiopathic nephrotic syndrome: Historical perspectives and lessons for the future. Nephrol Dial Transplant 2014;29:2207–16.CrossRefGoogle ScholarPubMed
Podesta, M. A., Ponticelli, C.. Autoimmunity in focal segmental glomerulosclerosis: A long-standing yet elusive association. Front Med (Lausanne) 2020;7:604961.Google Scholar
Wen, Y., Shah, S., Campbell, K. N.. Molecular mechanisms of proteinuria in focal segmental glomerulosclerosis. Front Med (Lausanne) 2018;5:98.Google Scholar
Vivarelli, M., Massella, L., Ruggiero, B., Emma, F.. Minimal change disease. Clin J Am Soc Nephrol 2017;12:332–45.CrossRefGoogle ScholarPubMed
Chanchlani, R., Parekh, R. S.. Ethnic differences in childhood nephrotic syndrome. Front Pediatr 2016;4:39.Google Scholar
Banh, T. H., Hussain-Shamsy, N., Patel, V., Vasilevska-Ristovska, J., Borges, K., Sibbald, C., et al. Ethnic differences in incidence and outcomes of childhood nephrotic syndrome. Clin J Am Soc Nephrol 2016;11:1760–8.Google Scholar
Mubarak, M., Kazi, J. I., Lanewala, A., Hashmi, S., Akhter, F.. Pathology of idiopathic nephrotic syndrome in children: Are the adolescents different from young children? Nephrol Dial Transplant 2012;27:722–6.CrossRefGoogle ScholarPubMed
Sadowski, C. E., Lovric, S., Ashraf, S., Pabst, W. L., Gee, H. Y., Kohl, S., et al. A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol 2015;26:1279–89.CrossRefGoogle ScholarPubMed
Trautmann, A., Bodria, M., Ozaltin, F., Gheisari, A., Melk, A., Azocar, M., et al. Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort. Clin J Am Soc Nephrol 2015;10:592–600.CrossRefGoogle ScholarPubMed
Liapis, H., Romagnani, P., Anders, H. J.. New insights into the pathology of podocyte loss: mitotic catastrophe. Am J Pathol 2013;183:1364–74.Google Scholar
Kriz, W., Shirato, I., Nagata, M., LeHir, M., Lemley, K. V.. The podocyte’s response to stress: The enigma of foot process effacement. Am J Physiol Renal Physiol 2013;304:F333–47.Google Scholar
Chen, Y. M., Liapis, H.. Focal segmental glomerulosclerosis: molecular genetics and targeted therapies. BMC Nephrol 2015;16:101.CrossRefGoogle ScholarPubMed
Haas, M., Seshan, S. V., Barisoni, L., Amann, K., Bajema, I. M., Becker, J. U., et al. Consensus definitions for glomerular lesions by light and electron microscopy: Recommendations from a working group of the Renal Pathology Society. Kidney Int 2020 98:1120–34.CrossRefGoogle Scholar
De Vriese, A. S., Sethi, S., Nath, K. A., Glassock, R. J., Fervenza, F. C.. Differentiating primary, genetic, and secondary FSGS in adults: A clinicopathologic approach. J Am Soc Nephrol 2018;29:759–74.CrossRefGoogle ScholarPubMed
Tullus, K., Webb, H., Bagga, A.. Management of steroid-resistant nephrotic syndrome in children and adolescents. Lancet Child Adolesc Health 2018;2:880–90.CrossRefGoogle ScholarPubMed
Rheault, M. N., Zhang, L., Selewski, D. T., Kallash, M., Tran, C. L., Seamon, M., et al. AKI in children hospitalized with nephrotic syndrome. Clin J Am Soc Nephrol 2015;10:2110–18.Google Scholar
Trautmann, A., Vivarelli, M., Samuel, S., Gipson, D., Sinha, A., Schaefer, F., et al. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 2020;35:1529–61.CrossRefGoogle ScholarPubMed
Buscher, A. K., Beck, B. B., Melk, A., Hoefele, J., Kranz, B., Bamborschke, D., et al. Rapid response to cyclosporin A and favorable renal outcome in nongenetic versus genetic steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 2016;11:245–53.CrossRefGoogle ScholarPubMed
Ranganathan, S.. Pathology of podocytopathies causing nephrotic syndrome in children. Front Pediatr 2016;4:32.Google Scholar
Bonsib., S. M Focal-segmental glomerulosclerosis. The relationship between tubular atrophy and segmental sclerosis. Am J Clin Pathol 1999;111(3):343–8.CrossRefGoogle ScholarPubMed
D’Agati, V.. Pathologic classification of focal segmental glomerulosclerosis. Semin Nephrol 2003;23:117–34.Google ScholarPubMed
D’Agati, V. D., Kaskel, F. J., Falk, R. J.. Focal segmental glomerulosclerosis. N Engl J Med 2011;365:2398–411.Google ScholarPubMed
Cossey, L. N., Larsen, C. P., Liapis, H.. Collapsing glomerulopathy: A 30-year perspective and single, large center experience. Clin Kidney J 2017;10(4):443–9.Google Scholar
Smeets, B., Stucker, F., Wetzels, J., Brocheriou, I., Ronco, P., Grone, H. J., et al. Detection of activated parietal epithelial cells on the glomerular tuft distinguishes early focal segmental glomerulosclerosis from minimal change disease. Am J Pathol 2014;184:3239–48.CrossRefGoogle ScholarPubMed
Vivarelli, M., Moscaritolo, E., Tsalkidis, A., Massella, L., Emma, F.. Time for initial response to steroids is a major prognostic factor in idiopathic nephrotic syndrome. J Pediatr 2010;156:965–71.Google Scholar
Mendonca, C., Oliveira, E. A., Froes, B. P., Faria, L. D., Pinto, J. S., Nogueira, M. M., et al. A predictive model of progressive chronic kidney disease in idiopathic nephrotic syndrome. Pediatr Nephrol 2015;30:2011–20.CrossRefGoogle ScholarPubMed
Larkins, N. G., Liu, I. D., Willis, N. S., Craig, J. C., Hodson, E. M.. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev 2020;4:CD002290.Google Scholar
McCaffrey, J., Lennon, R., Webb, N. J.. The non-immunosuppressive management of childhood nephrotic syndrome. Pediatr Nephrol 2016;31:1383–402.Google Scholar
Banerjee, S., Dissanayake, P. V., Abeyagunawardena, A. S.. Vaccinations in children on immunosuppressive medications for renal disease. Pediatr Nephrol 2016;31:1437–48.Google Scholar
Rovin, B. H., Caster, D. J., Cattran, D. C., Gibson, K. L., Hogan, J. J., Moeller, M. J., et al. Management and treatment of glomerular diseases (part 2): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 2019;95:281–95.Google Scholar
Chua, A., Cramer, C., Moudgil, A., Martz, K., Smith, J., Blydt-Hansen, T., et al. Kidney transplant practice patterns and outcome benchmarks over 30 years: The 2018 report of the NAPRTCS. Pediatr Transplant 2019;23:e13597.Google Scholar
Bouts, A., Veltkamp, F., Tonshoff, B., Vivarelli, M., Members of the Working Group “Transplantation”, “Idiopathic Nephrotic Syndrome” of the European Society of Pediatric Nephrology. European Society of Pediatric Nephrology survey on current practice regarding recurrent focal segmental glomerulosclerosis after pediatric kidney transplantation. Pediatr Transplant 2019;23:e13385.CrossRefGoogle ScholarPubMed
Altassan, R., Witters, P., Saifudeen, Z., Quelhas, D., Jaeken, J., Levtchenko, E., et al. Renal involvement in PMM2-CDG, a mini-review. Mol Genet Metab 2018;123:292–6.CrossRefGoogle ScholarPubMed
Liapis, H.. Molecular pathology of nephrotic syndrome in childhood: a contemporary approach to diagnosis. Pediatr Dev Pathol 2008;11:154–63.CrossRefGoogle ScholarPubMed
Gbadegesin, R., Hinkes, B. G., Hoskins, B. E., Vlangos, C. N., Heeringa, S. F., Liu, J., et al. Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS). Nephrol Dial Transplant 2008;23:1291–7.Google Scholar
Kemper, M. J., Lemke, A.. Treatment of genetic forms of nephrotic syndrome. Front Pediatr 2018;6:72.Google Scholar
Nagatani, K., Hayashi, M.. Combination therapy improves pathology indices in diffuse mesangial sclerosis. Pediatr Int 2019;61:517–20.CrossRefGoogle ScholarPubMed
Sajantila, A., Salem, A. H., Savolainen, P., Bauer, K., Gierig, C., Paabo, S.. Paternal and maternal DNA lineages reveal a bottleneck in the founding of the Finnish population. Proc Natl Acad Sci U S A 1996;93:12035–9.Google Scholar
Hinkes, B. G., Mucha, B., Vlangos, C. N. et al.; Arbeitsgemeinschaft für Paediatrische Nephrologie Study Group. Nephrotic syndrome in the first year of life: Two thirds of cases are caused by mutations in 4 genes (NPHS1, NPHS2, WT1, and LAMB2). Pediatrics 2007;119(4):e907–19.CrossRefGoogle ScholarPubMed
Caridi, G., Bertelli, R., Di Duca, M., Dagnino, M., Emma, F., Onetti Muda, A., et al. Broadening the spectrum of diseases related to podocin mutations. J Am Soc Nephrol 2003;14:1278–86.Google Scholar
Boute, N., Gribouval, O., Roselli, S., Benessy, F., Lee, H., Fuchshuber, A., et al. NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet 2000;24:349–54.Google Scholar
Bierzynska, A., McCarthy, H. J., Soderquest, K., Sen, E. S., Colby, E., Ding, W. Y., et al. Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management. Kidney Int 2017;91:937–47.CrossRefGoogle ScholarPubMed
Lovric, S., Ashraf, S., Tan, W., Hildebrandt, F.. Genetic testing in steroid-resistant nephrotic syndrome: when and how? Nephrol Dial Transplant 2016;31:1802–13.Google Scholar
Ovunc, B., Ashraf, S., Vega-Warner, V., Bockenhauer, D., Elshakhs, N. A., Joseph, M., et al. Mutation analysis of NPHS1 in a worldwide cohort of congenital nephrotic syndrome patients. Nephron Clin Pract 2012;120:c139–46.Google Scholar
Romppanen, E. L., Mononen, I.. Detection of the Finnish-type congenital nephrotic syndrome by restriction fragment length polymorphism and dual-color oligonucleotide ligation assays. Clin Chem 2000;46:811–16.Google Scholar
Patrakka, J., Kestila, M., Wartiovaara, J., Ruotsalainen, V., Tissari, P., Lenkkeri, U., et al. Congenital nephrotic syndrome (NPHS1): Features resulting from different mutations in Finnish patients. Kidney Int 2000;58:972–80.Google Scholar
Zhuo, L., Huang, L., Yang, Z., Li, G., Wang, L.. A comprehensive analysis of NPHS1 gene mutations in patients with sporadic focal segmental glomerulosclerosis. BMC Med Genet 2019;20:111.Google Scholar
Roselli, S., Gribouval, O., Boute, N., Sich, M., Benessy, F., Attie, T., et al. Podocin localizes in the kidney to the slit diaphragm area. Am J Pathol 2002;160:131–19.Google Scholar
Huber, T. B., Kottgen, M., Schilling, B., Walz, G., Benzing, T.. Interaction with podocin facilitates nephrin signaling. J Biol Chem 2001;276:41543–6.Google Scholar
Sen, E. S., Dean, P., Yarram-Smith, L., Bierzynska, A., Woodward, G., Buxton, C., et al. Clinical genetic testing using a custom-designed steroid-resistant nephrotic syndrome gene panel: analysis and recommendations. J Med Genet 2017;54:795–804.CrossRefGoogle ScholarPubMed
Tory, K., Menyhard, D. K., Woerner, S., Nevo, F., Gribouval, O., Kerti, A., et al. Mutation-dependent recessive inheritance of NPHS2-associated steroid-resistant nephrotic syndrome. Nat Genet 2014;46:299–304.Google Scholar
Frishberg, Y., Rinat, C., Megged, O., Shapira, E., Feinstein, S., Raas-Rothschild, A.. Mutations in NPHS2 encoding podocin are a prevalent cause of steroid-resistant nephrotic syndrome among Israeli-Arab children. J Am Soc Nephrol 2002;13:400–5.Google Scholar
Rood, I. M., Deegens, J. K. J., Lugtenberg, D., Bongers, E., Wetzels, J. F. M.. Nephrotic syndrome with mutations in NPHS2: The role of R229Q and implications for genetic counseling. Am J Kidney Dis 2019;73:400–3.Google Scholar
Holmberg, C., Jalanko, H.. Congenital nephrotic syndrome and recurrence of proteinuria after renal transplantation. Pediatr Nephrol 2014;29:2309–17.Google Scholar
Wang, S. X., Ahola, H., Palmen, T., Solin, M. L., Luimula, P., Holthofer, H.. Recurrence of nephrotic syndrome after transplantation in CNF is due to autoantibodies to nephrin. Exp Nephrol 2001;9:327–31.CrossRefGoogle ScholarPubMed
Becker-Cohen, R., Bruschi, M., Rinat, C., Feinstein, S., Zennaro, C., Ghiggeri, G. M., et al. Recurrent nephrotic syndrome in homozygous truncating NPHS2 mutation is not due to anti-podocin antibodies. Am J Transplant 2007;7:256–60.Google Scholar
Billing, H., Muller, D., Ruf, R., Lichtenberger, A., Hildebrandt, F., August, C., et al. NPHS2 mutation associated with recurrence of proteinuria after transplantation. Pediatr Nephrol 2004;19:561–4.Google Scholar
Warejko, J. K., Tan, W., Daga, A., Schapiro, D., Lawson, J. A., Shril, S., et al. Whole exome sequencing of patients with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 2018;13:53–62.Google Scholar
Varner, J. D., Chryst-Stangl, M., Esezobor, C. I., Solarin, A., Wu, G., Lane, B., et al. Genetic testing for steroid-resistant-nephrotic syndrome in an outbred population. Front Pediatr 2018;6:307.Google Scholar
Gulati, A., Sharma, A., Hari, P., Dinda, A. K., Bagga, A.. Idiopathic collapsing glomerulopathy in children. Clin Exp Nephrol 2008;12:348–53.CrossRefGoogle ScholarPubMed
Haas, M.. Collapsing glomerulopathy: Many means to a similar end. Kidney Int 2008;73:669–71.Google Scholar
Chandra, P., Kopp, J. B.. Viruses and collapsing glomerulopathy: A brief critical review. Clin Kidney J 2013;6:1–5.CrossRefGoogle ScholarPubMed
Salvatore, S. P., Barisoni, L. M., Herzenberg, A. M., Chander, P. N., Nickeleit, V., Seshan, S. V.. Collapsing glomerulopathy in 19 patients with systemic lupus erythematosus or lupus-like disease. Clin J Am Soc Nephrol 2012;7:914–25.CrossRefGoogle ScholarPubMed
Markowitz, G. S., Nasr, S. H., Stokes, M. B., D’Agati, V. D.. Treatment with IFN-α, -β, or -γ is associated with collapsing focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 2010;5:607–15.CrossRefGoogle ScholarPubMed
ten Dam, M. A., Hilbrands, L. B., Wetzels, J. F.. Nephrotic syndrome induced by pamidronate. Med Oncol 2011;28:1196–200.Google Scholar
Herlitz, L. C., Markowitz, G. S., Farris, A. B., Schwimmer, J. A., Stokes, M. B., Kunis, C., et al. Development of focal segmental glomerulosclerosis after anabolic steroid abuse. J Am Soc Nephrol 2010;21:163–72.Google Scholar
Abid, Q., Best Rocha, A., Larsen, C. P., Schulert, G., Marsh, R., Yasin, S., et al. APOL1-associated collapsing focal segmental glomerulosclerosis in a patient with stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI). Am J Kidney Dis 2020;75:287–90.Google Scholar
Swaminathan, S., Lager, D. J., Qian, X., Stegall, M. D., Larson, T. S., Griffin, M. D.. Collapsing and non-collapsing focal segmental glomerulosclerosis in kidney transplants. Nephrol Dial Transplant 2006;21:2607–14.CrossRefGoogle ScholarPubMed
Ray, P. E., Li, J., Das, J. R., Tang, P.. Childhood HIV-associated nephropathy: 36 years later. Pediatr Nephrol 2021;36:2189–201.Google Scholar
Velez, J. C. Q., Caza, T., Larsen, C. P.. COVAN is the new HIVAN: The re-emergence of collapsing glomerulopathy with COVID-19. Nat Rev Nephrol 2020;16:565–7.Google Scholar
Genovese, G., Friedman, D. J., Ross, M. D., Lecordier, L., Uzureau, P., Freedman, B. I., et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 2010;329:841–5.Google Scholar
Limou, S., Nelson, G. W., Kopp, J. B., Winkler, C. A.. APOL1 kidney risk alleles: Population genetics and disease associations. Adv Chronic Kidney Dis 2014;21:426–33.CrossRefGoogle ScholarPubMed
Friedman, D. J., Pollak, M. R.. APOL1 nephropathy: From genetics to clinical applications. Clin J Am Soc Nephrol 2021;16:294–303.CrossRefGoogle ScholarPubMed
Sethna, C. B., Gipson, D. S.. Treatment of FSGS in children. Adv Chronic Kidney Dis 2014;21:194–9.CrossRefGoogle ScholarPubMed
El-Refaey, A. M., Kapur, G., Jain, A., Hidalgo, G., Imam, A., Valentini, R. P., et al. Idiopathic collapsing focal segmental glomerulosclerosis in pediatric patients. Pediatr Nephrol 2007;22:396–402.Google Scholar
Valeri, A., Barisoni, L., Appel, G. B., Seigle, R., D’Agati, V.. Idiopathic collapsing focal segmental glomerulosclerosis: A clinicopathologic study. Kidney Int 1996;50:1734–46.CrossRefGoogle ScholarPubMed
Fiorentino, F., Napoletano, S., Caiazzo, F., Sessa, M., Bono, S., Spizzichino, L., et al. Chromosomal microarray analysis as a first-line test in pregnancies with a priori low risk for the detection of submicroscopic chromosomal abnormalities. Eur J Hum Genet 2013;21:725–30.Google Scholar
Verbitsky, M., Westland, R., Perez, A., Kiryluk, K., Liu, Q., Krithivasan, P., et al. The copy number variation landscape of congenital anomalies of the kidney and urinary tract. Nat Genet 2019;51:117–27.Google Scholar
Li, S., Han, X., Wang, Y., Chen, S., Niu, J., Qian, Z., et al. Chromosomal microarray analysis in fetuses with congenital anomalies of the kidney and urinary tract: A prospective cohort study and meta-analysis. Prenat Diagn 2019;39:165–74.Google Scholar
Tayeh, M. K., Chin, E. L., Miller, V. R., Bean, L. J., Coffee, B., Hegde, M.. Targeted comparative genomic hybridization array for the detection of single- and multiexon gene deletions and duplications. Genet Med 2009;11:232–40.Google Scholar
Zheng, M., Tian, S. Z., Capurso, D., Kim, M., Maurya, R., Lee, B., et al. Multiplex chromatin interactions with single-molecule precision. Nature 2019;566:558–62.Google Scholar
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405–24.Google Scholar
Kaplan, J. M., Kim, S. H., North, K. N., Rennke, H., Correia, L. A., Tong, H. Q., et al. Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. Nat Genet 2000;24:251–6.Google Scholar
Bartram, M. P., Habbig, S., Pahmeyer, C., Hohne, M., Weber, L. T., Thiele, H., et al. Three-layered proteomic characterization of a novel ACTN4 mutation unravels its pathogenic potential in FSGS. Hum Mol Genet 2016;25:1152–64.Google Scholar
Oegema, K., Savoian, M. S., Mitchison, T. J., Field, C. M.. Functional analysis of a human homologue of the Drosophila actin binding protein anillin suggests a role in cytokinesis. J Cell Biol 2000;150:539–52.CrossRefGoogle ScholarPubMed
Gbadegesin, R. A., Hall, G., Adeyemo, A., Hanke, N., Tossidou, I., Burchette, J., et al. Mutations in the gene that encodes the F-actin binding protein anillin cause FSGS. J Am Soc Nephrol 2014;25:1991–2002.Google Scholar
Akilesh, S., Suleiman, H., Yu, H., Stander, M. C., Lavin, P., Gbadegesin, R., et al. Arhgap24 inactivates Rac1 in mouse podocytes, and a mutant form is associated with familial focal segmental glomerulosclerosis. J Clin Invest 2011;121:4127–37.CrossRefGoogle Scholar
Gigante, M., Pontrelli, P., Montemurno, E., Roca, L., Aucella, F., Penza, R., et al. CD2AP mutations are associated with sporadic nephrotic syndrome and focal segmental glomerulosclerosis (FSGS). Nephrol Dial Transplant 2009;24:1858–64.Google Scholar
Takano, T., Bareke, E., Takeda, N., Aoudjit, L., Baldwin, C., Pisano, P., et al. Recessive mutation in CD2AP causes focal segmental glomerulosclerosis in humans and mice. Kidney Int 2019;95:57–61.Google Scholar
Lowik, M. M., Groenen, P. J., Pronk, I., Lilien, M. R., Goldschmeding, R., Dijkman, H. B., et al. Focal segmental glomerulosclerosis in a patient homozygous for a CD2AP mutation. Kidney Int 2007;72:1198–203.Google Scholar
Boyer, O., Nevo, F., Plaisier, E., Funalot, B., Gribouval, O., Benoit, G., et al. INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy. N Engl J Med 2011;365:2377–88.Google Scholar
Dong, F., Li, S., Pujol-Moix, N., Luban, N. L., Shin, S. W., Seo, J. H., et al. Genotype-phenotype correlation in MYH9-related thrombocytopenia. Br J Haematol 2005;130:620–7.CrossRefGoogle ScholarPubMed
Tabibzadeh, N., Fleury, D., Labatut, D., Bridoux, F., Lionet, A., Jourde-Chiche, N., et al. MYH9-related disorders display heterogeneous kidney involvement and outcome. Clin Kidney J 2019;12:494–502.Google Scholar
Hall, G., Wang, L., Spurney, R. F.. TRPC channels in proteinuric kidney diseases. Cells 2019;9: 44.CrossRefGoogle ScholarPubMed
Winn, M. P., Conlon, P. J., Lynn, K. L., Farrington, M. K., Creazzo, T., Hawkins, A. F., et al. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science 2005;308:1801–4.CrossRefGoogle ScholarPubMed
Reiser, J., Polu, K. R., Moller, C. C., Kenlan, P., Altintas, M. M., Wei, C., et al. TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. Nat Genet 2005;37:739–44.CrossRefGoogle ScholarPubMed
Xiong, S., Shuai, L., Li, X., Dang, X., Wu, X., He, Q.. Podocytic infolding in Schimke immuno-osseous dysplasia with novel SMARCAL1 mutations: A case report. BMC Nephrol 2020;21:170.CrossRefGoogle ScholarPubMed
Okumura, T., Furuichi, K., Higashide, T., Sakurai, M., Hashimoto, S., Shinozaki, Y., et al. Association of PAX2 and other gene mutations with the clinical manifestations of renal coloboma syndrome. PLoS ONE 2015;10:e0142843.Google Scholar
Vivante, A., Chacham, O. S., Shril, S., Schreiber, R., Mane, S. M., Pode-Shakked, B., et al. Dominant PAX2 mutations may cause steroid-resistant nephrotic syndrome and FSGS in children. Pediatr Nephrol 2019;34:1607–13.Google Scholar
Stefanidis, C. J., Querfeld, U.. The podocyte as a target: Cyclosporin A in the management of the nephrotic syndrome caused by WT1 mutations. Eur J Pediatr 2011;170:1377–83.Google Scholar
Barbaux, S., Niaudet, P., Gubler, M. C., Grunfeld, J. P., Jaubert, F., Kuttenn, F., et al. Donor splice-site mutations in WT1 are responsible for Frasier syndrome. Nat Genet 1997;17:467–70.Google Scholar
Denamur, E., Bocquet, N., Mougenot, B., Da Silva, F., Martinat, L., Loirat, C., et al. Mother-to-child transmitted WT1 splice-site mutation is responsible for distinct glomerular diseases. J Am Soc Nephrol 1999;10:2219–23.Google Scholar
Demmer, L., Primack, W., Loik, V., Brown, R., Therville, N., McElreavey, K.. Frasier syndrome: A cause of focal segmental glomerulosclerosis in a 46,XX female. J Am Soc Nephrol 1999;10:2215–18.Google Scholar
Gee, H. Y., Saisawat, P., Ashraf, S., Hurd, T. W., Vega-Warner, V., Fang, H., et al. ARHGDIA mutations cause nephrotic syndrome via defective RHO GTPase signaling. J Clin Invest 2013;123:3243–53.Google Scholar
Korkmaz, E., Lipska-Zietkiewicz, B. S., Boyer, O., Gribouval, O., Fourrage, C., Tabatabaei, M., et al. ADCK4-associated glomerulopathy causes adolescence-onset FSGS. J Am Soc Nephrol 2016;27:63–8.Google Scholar
Rao, J., Ashraf, S., Tan, W., van der Ven, A. T., Gee, H. Y., Braun, D. A., et al. Advillin acts upstream of phospholipase C 1 in steroid-resistant nephrotic syndrome. J Clin Invest 2017;127:4257–69.Google Scholar
Ebarasi, L., Ashraf, S., Bierzynska, A., Gee, H. Y., McCarthy, H. J., Lovric, S., et al. Defects of CRB2 cause steroid-resistant nephrotic syndrome. Am J Hum Genet 2015;96:153–61.Google Scholar
Slavotinek, A., Kaylor, J., Pierce, H., Cahr, M., DeWard, S. J., Schneidman-Duhovny, D., et al. CRB2 mutations produce a phenotype resembling congenital nephrosis, Finnish type, with cerebral ventriculomegaly and raised alpha-fetoprotein. Am J Hum Genet 2015;96:162–9.CrossRefGoogle ScholarPubMed
Gee, H. Y., Sadowski, C. E., Aggarwal, P. K., Porath, J. D., Yakulov, T. A., Schueler, M., et al. FAT1 mutations cause a glomerulotubular nephropathy. Nat Commun 2016;7:10822.Google Scholar
Gee, H. Y., Zhang, F., Ashraf, S., Kohl, S., Sadowski, C. E., Vega-Warner, V., et al. KANK deficiency leads to podocyte dysfunction and nephrotic syndrome. J Clin Invest 2015;125:2375–84.Google Scholar
Balbas, M. D., Burgess, M. R., Murali, R., Wongvipat, J., Skaggs, B. J., Mundel, P., et al. MAGI-2 scaffold protein is critical for kidney barrier function. Proc Natl Acad Sci U S A 2014;111:14876–81.Google Scholar
Bierzynska, A., Soderquest, K., Dean, P., Colby, E., Rollason, R., Jones, C., et al. MAGI2 mutations cause congenital nephrotic syndrome. J Am Soc Nephrol 2017;28:1614–21.Google Scholar
Mele, C., Iatropoulos, P., Donadelli, R., Calabria, A., Maranta, R., Cassis, P., et al. MYO1E mutations and childhood familial focal segmental glomerulosclerosis. N Engl J Med 2011;365:295–306.Google Scholar
Hashmi, J. A., Safar, R. A., Afzal, S., Albalawi, A. M., Abdu-Samad, F., Iqbal, Z., et al. Whole exome sequencing identification of a novel insertion mutation in the phospholipase C epsilon1 gene in a family with steroid resistant inherited nephrotic syndrome. Mol Med Rep 2018;18:5095–100.Google Scholar
Tasic, V., Gucev, Z., Polenakovic, M.. Steroid resistant nephrotic syndrome-genetic consideration. Pril (Makedon Akad Nauk Umet Odd Med Nauki) 2015;36:5–12.Google Scholar
Ozaltin, F., Ibsirlioglu, T., Taskiran, E. Z., Baydar, D. E., Kaymaz, F., Buyukcelik, M., et al. Disruption of PTPRO causes childhood-onset nephrotic syndrome. Am J Hum Genet 2011;89:139–47.Google Scholar
Ashraf, S., Gee, H. Y., Woerner, S., Xie, L. X., Vega-Warner, V., Lovric, S., et al. ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption. J Clin Invest 2013;123:5179–89.Google Scholar
Quinzii, C., Naini, A., Salviati, L., Trevisson, E., Navas, P., Dimauro, S., et al. A mutation in para-hydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency. Am J Hum Genet 2006;78:345–9.Google Scholar
Lopez, L. C., Schuelke, M., Quinzii, C. M., Kanki, T., Rodenburg, R. J., Naini, A., et al. Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations. Am J Hum Genet 2006;79:1125–9.CrossRefGoogle ScholarPubMed
Hermle, T., Schneider, R., Schapiro, D., Braun, D. A., van der Ven, A. T., Warejko, J. K., et al. GAPVD1 and ANKFY1 mutations implicate RAB5 regulation in nephrotic syndrome. J Am Soc Nephrol 2018;29:2123–38.Google Scholar
Wan, X., Chen, Z., Choi, W. I., Gee, H. Y., Hildebrandt, F., Zhou, W.. Loss of epithelial membrane protein 2 aggravates podocyte injury via upregulation of caveolin-1. J Am Soc Nephrol 2016;27:1066–75.Google Scholar
Gee, H. Y., Ashraf, S., Wan, X., Vega-Warner, V., Esteve-Rudd, J., Lovric, S., et al. Mutations in EMP2 cause childhood-onset nephrotic syndrome. Am J Hum Genet 2014;94:884–90.Google Scholar
van Berkel, Y., Ludwig, M., van Wijk, J. A. E., Bokenkamp, A.. Proteinuria in Dent disease: A review of the literature. Pediatr Nephrol 2017;32:1851–9.CrossRefGoogle ScholarPubMed
Dorval, G., Kuzmuk, V., Gribouval, O., Welsh, G. I., Bierzynska, A., Schmitt, A., et al. TBC1D8B loss-of-function mutations lead to X-linked nephrotic syndrome via defective trafficking pathways. Am J Hum Genet 2019;104:348–55.Google Scholar
Sanna-Cherchi, S., Burgess, K. E., Nees, S. N., Caridi, G., Weng, P. L., Dagnino, M., et al. Exome sequencing identified MYO1E and NEIL1 as candidate genes for human autosomal recessive steroid-resistant nephrotic syndrome. Kidney Int 2011;80:389–96.Google Scholar
Has, C., Sparta, G., Kiritsi, D., Weibel, L., Moeller, A., Vega-Warner, V., et al. Integrin alpha3 mutations with kidney, lung, and skin disease. N Engl J Med 2012;366:1508–14.Google Scholar
Kambham, N., Tanji, N., Seigle, R. L., Markowitz, G. S., Pulkkinen, L., Uitto, J., et al. Congenital focal segmental glomerulosclerosis associated with beta4 integrin mutation and epidermolysis bullosa. Am J Kidney Dis 2000;36:190–6.Google Scholar
Berkovic, S. F., Dibbens, L. M., Oshlack, A., Silver, J. D., Katerelos, M., Vears, D. F., et al. Array-based gene discovery with three unrelated subjects shows SCARB2/LIMP-2 deficiency causes myoclonus epilepsy and glomerulosclerosis. Am J Hum Genet 2008;82:673–84.Google Scholar
Prasad, R., Hadjidemetriou, I., Maharaj, A., Meimaridou, E., Buonocore, F., Saleem, M., et al. Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome. J Clin Invest 2017;127:942–53.CrossRefGoogle ScholarPubMed
Davis, E. E., Zhang, Q., Liu, Q., Diplas, B. H., Davey, L. M., Hartley, J., et al. TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum. Nat Genet 2011;43:189–96.Google Scholar
Bullich, G., Vargas, I., Trujillano, D., Mendizabal, S., Pinero-Fernandez, J. A., Fraga, G., et al. Contribution of the TTC21B gene to glomerular and cystic kidney diseases. Nephrol Dial Transplant 2017;32:151–6.Google ScholarPubMed
Huynh Cong, E., Bizet, A. A., Boyer, O., Woerner, S., Gribouval, O., Filhol, E., et al. A homozygous missense mutation in the ciliary gene TTC21B causes familial FSGS. J Am Soc Nephrol 2014;25:2435–43.Google Scholar
Braun, D. A., Rao, J., Mollet, G., Schapiro, D., Daugeron, M. C., Tan, W., et al. Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly. Nat Genet 2017;49:1529–38.Google Scholar
Shaheen, R., Abdel-Salam, G. M., Guy, M. P., Alomar, R., Abdel-Hamid, M. S., Afifi, H. H., et al. Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism. Genome Biol 2015;16:210.Google Scholar
Rosti, R. O., Sotak, B. N., Bielas, S. L., Bhat, G., Silhavy, J. L., Aslanger, A. D., et al. Homozygous mutation in NUP107 leads to microcephaly with steroid-resistant nephrotic condition similar to Galloway-Mowat syndrome. J Med Genet 2017;54:399–403.Google Scholar
Fujita, A., Tsukaguchi, H., Koshimizu, E., Nakazato, H., Itoh, K., Kuraoka, S., et al. Homozygous splicing mutation in NUP133 causes Galloway-Mowat syndrome. Ann Neurol 2018;84:814–28.Google Scholar
Jinks, R. N., Puffenberger, E. G., Baple, E., Harding, B., Crino, P., Fogo, A. B., et al. Recessive nephrocerebellar syndrome on the Galloway-Mowat syndrome spectrum is caused by homozygous protein-truncating mutations of WDR73. Brain 2015;138:2173–90.Google Scholar
Braun, D. A., Sadowski, C. E., Kohl, S., Lovric, S., Astrinidis, S. A., Pabst, W. L., et al. Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome. Nat Genet 2016;48:457–65.Google Scholar
Braun, D. A., Lovric, S., Schapiro, D., Schneider, R., Marquez, J., Asif, M., et al. Mutations in multiple components of the nuclear pore complex cause nephrotic syndrome. J Clin Invest 2018;128:4313–28.Google Scholar
Watts, A. J. B., Keller, K. H, Lerner, G., Rosales, I., Collins, A.B., Sekulic, M., et al. Discovery of autoantibodies targeting nephrin in minimal change disease supports a novel autoimmune etiology. J Am Soc Nephrol 2022;33:238–52.Google Scholar

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