Idiopathic Nephrotic Syndrome in Children: Genetic Aspects

  • Olivia Boyer
  • Kálmán Tory
  • Eduardo Machuca
  • Corinne Antignac
Living reference work entry

Abstract

Gene discovery efforts aimed at unraveling the causes of Mendelian forms of nephrotic syndrome have resulted in the identification of mutations in approximately 30 genes. These discoveries have helped decipher the pathophysiologic mechanisms of the glomerular filtration process by revealing that most of the defective proteins are essential for glomerular podocyte function. NPHS1 and NPHS2 encoding nephrin and podocin respectively are by far the two main genes implicated in SRNS, and mutations in INF2 encoding the formin INF2 are the most common cause of autosomal dominant focal segmental glomerulosclerosis. The accessibility to next generation-sequencing techniques has deeply facilitated the screening of mutations in a broader approach of podocyte-specific genes and has widened the phenotypes associated with podocyte gene mutations. Genetic diagnosis is necessary to allow for accurate genetic counseling, to avoid ineffective therapies and even start early suitable treatment, and hopefully in the near future, to offer specific mutation-based therapies.

Keywords

Nephrotic Syndrome Glomerular Basement Membrane Epidermolysis Bullosa Slit Diaphragm Autosomal Dominant 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Hinkes BG, Mucha B, Vlangos CN, Gbadegesin R, Liu J, Hasselbacher K, et al. 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.PubMedGoogle Scholar
  2. 2.
    Sadowski CE, Lovric S, Ashraf S, Pabst WL, Gee HY, Kohl S, et al. A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2014 [epub ahead of print].Google Scholar
  3. 3.
    Weber S, Gribouval O, Esquivel EL, Moriniere V, Tete MJ, Legendre C, et al. NPHS2 mutation analysis shows genetic heterogeneity of steroid-resistant nephrotic syndrome and low post-transplant recurrence. Kidney Int. 2004;66(2):571–9.PubMedGoogle Scholar
  4. 4.
    Ruf RG, Lichtenberger A, Karle SM, Haas JP, Anacleto FE, Schultheiss M, et al. Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome. J Am Soc Nephrol. 2004;15(3):722–32.PubMedGoogle Scholar
  5. 5.
    Winn MP. 2007 Young Investigator Award: TRP’ing into a new era for glomerular disease. J Am Soc Nephrol. 2008;19(6):1071–5.PubMedGoogle Scholar
  6. 6.
    Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S, Delfgaauw J, et al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med. 2008;14(9):931–8.PubMedCentralPubMedGoogle Scholar
  7. 7.
    Buscher AK, Kranz B, Buscher R, Hildebrandt F, Dworniczak B, Pennekamp P, et al. Immunosuppression and renal outcome in congenital and pediatric steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2010;5(11):2075–84.PubMedCentralPubMedGoogle Scholar
  8. 8.
    Ruf RG, Schultheiss M, Lichtenberger A, Karle SM, Zalewski I, Mucha B, et al. Prevalence of WT1 mutations in a large cohort of patients with steroid-resistant and steroid-sensitive nephrotic syndrome. Kidney Int. 2004;66(2):564–70.PubMedGoogle Scholar
  9. 9.
    Santin S, Bullich G, Tazon-Vega B, Garcia-Maset R, Gimenez I, Silva I, et al. Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2011;17.Google Scholar
  10. 10.
    Santin S, Tazon-Vega B, Silva I, Cobo MA, Gimenez I, Ruiz P, et al. Clinical value of NPHS2 analysis in early- and adult-onset steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2011;6(2):344–54.PubMedCentralPubMedGoogle Scholar
  11. 11.
    Pollak MR. Familial FSGS. Adv Chronic Kidney Dis. 2014;21(5):422–5.PubMedGoogle Scholar
  12. 12.
    Buscher AK, Weber S. Educational paper: the podocytopathies. Eur J Pediatr. 2012;171(8):1151–60.PubMedGoogle Scholar
  13. 13.
    Saleem MA. New developments in steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2013;28(5):699–709.PubMedGoogle Scholar
  14. 14.
    Kestila M, Lenkkeri U, Mannikko M, Lamerdin J, McCready P, Putaala H, et al. Positionally cloned gene for a novel glomerular protein–nephrin–is mutated in congenital nephrotic syndrome. Mol Cell. 1998;1(4):575–82.PubMedGoogle Scholar
  15. 15.
    Philippe A, Nevo F, Esquivel EL, Reklaityte D, Gribouval O, Tete MJ, et al. Nephrin mutations can cause childhood-onset steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2008;19:1871–78.Google Scholar
  16. 16.
    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(4):349–54.PubMedGoogle Scholar
  17. 17.
    Conlon PJ, Butterly D, Albers F, Rodby R, Gunnells JC, Howell DN. Clinical and pathologic features of familial focal segmental glomerulosclerosis. Am J Kidney Dis. 1995;26(1):34–40.PubMedGoogle Scholar
  18. 18.
    Rana K, Isbel N, Buzza M, Dagher H, Henning P, Kainer G, et al. Clinical, histopathologic, and genetic studies in nine families with focal segmental glomerulosclerosis. Am J Kidney Dis. 2003;41(6):1170–8.PubMedGoogle Scholar
  19. 19.
    Cong EH, Bizet AA, 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(11):2435–43.Google Scholar
  20. 20.
    Barua M, Stellacci E, Stella L, Weins A, Genovese G, Muto V, et al. Mutations in PAX2 associate with adult-onset FSGS. J Am Soc Nephrol. 2014;25(9):1942–53.PubMedGoogle Scholar
  21. 21.
    Bullich G, Trujillano D, Santin S, Ossowski S, Mendizabal S, Fraga G, et al. Targeted next-generation sequencing in steroid-resistant nephrotic syndrome: mutations in multiple glomerular genes may influence disease severity. Eur J Hum Genet. 2014 [epub ahead of print].Google Scholar
  22. 22.
    Lovric S, Fang H, Vega-Warner V, Sadowski CE, Gee HY, Halbritter J, et al. Rapid detection of monogenic causes of childhood-onset steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2014;9(6):1109–16.PubMedCentralPubMedGoogle Scholar
  23. 23.
    Hinkes B, Vlangos C, Heeringa S, Mucha B, Gbadegesin R, Liu J, et al. Specific podocin mutations correlate with age of onset in steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2008;19(2):365–71.PubMedCentralPubMedGoogle Scholar
  24. 24.
    Karle SM, Uetz B, Ronner V, Glaeser L, Hildebrandt F, Fuchshuber A. Novel mutations in NPHS2 detected in both familial and sporadic steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2002;13(2):388–93.PubMedGoogle Scholar
  25. 25.
    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(5):1278–86.PubMedGoogle Scholar
  26. 26.
    Hinkes B, Vlangos C, Heeringa S, Mucha B, Gbadegesin R, Liu J, et al. Specific podocin mutations correlate with age of onset in steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2008;19(2):365–71.PubMedCentralPubMedGoogle Scholar
  27. 27.
    Bouchireb K, Boyer O, Gribouval O, Nevo F, Huynh-Cong E, Moriniere V, et al. NPHS2 mutations in steroid-resistant nephrotic syndrome: a mutation update and the associated phenotypic spectrum. Hum Mutat. 2014;35(2):178–86.PubMedGoogle Scholar
  28. 28.
    Machuca E, Benoit G, Nevo F, Tete MJ, Gribouval O, Pawtowski A, et al. Genotype-phenotype correlations in non-Finnish congenital nephrotic syndrome. J Am Soc Nephrol. 2010;21(7):1209–17.PubMedCentralPubMedGoogle Scholar
  29. 29.
    He N, Zahirieh A, Mei Y, Lee B, Senthilnathan S, Wong B, et al. Recessive NPHS2 (Podocin) mutations are rare in adult-onset idiopathic focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2007;2(1):31–7.PubMedGoogle Scholar
  30. 30.
    McKenzie LM, Hendrickson SL, Briggs WA, Dart RA, Korbet SM, Mokrzycki MH, et al. NPHS2 variation in sporadic focal segmental glomerulosclerosis. J Am Soc Nephrol. 2007;18(11):2987–95.PubMedCentralPubMedGoogle Scholar
  31. 31.
    Aucella F, De Bonis P, Gatta G, Muscarella LA, Vigilante M, di Giorgio G, et al. Molecular analysis of NPHS2 and ACTN4 genes in a series of 33 Italian patients affected by adult-onset nonfamilial focal segmental glomerulosclerosis. Nephron Clin Pract. 2005;99(2):c31–6.PubMedGoogle Scholar
  32. 32.
    Monteiro EJ, Pereira AC, Pereira AB, Krieger JE, Mastroianni-Kirsztajn G. NPHS2 mutations in adult patients with primary focal segmental glomerulosclerosis. J Nephrol. 2006;19(3):366–71.PubMedGoogle Scholar
  33. 33.
    Tonna SJ, Needham A, Polu K, Uscinski A, Appel GB, Falk RJ, et al. NPHS2 variation in focal and segmental glomerulosclerosis. BMC Nephrol. 2008;9:13.PubMedCentralPubMedGoogle Scholar
  34. 34.
    Tsukaguchi H, Sudhakar A, Le TC, Nguyen T, Yao J, Schwimmer JA, et al. NPHS2 mutations in late-onset focal segmental glomerulosclerosis: R229Q is a common disease-associated allele. J Clin Invest. 2002;110(11):1659–66.PubMedCentralPubMedGoogle Scholar
  35. 35.
    Tsukaguchi H, Yager H, Dawborn J, Jost L, Cohlmia J, Abreu PF, et al. A locus for adolescent and adult onset familial focal segmental glomerulosclerosis on chromosome 1q25-31. J Am Soc Nephrol. 2000;11(9):1674–80.PubMedGoogle Scholar
  36. 36.
    Machuca E, Hummel A, Nevo F, Dantal J, Martinez F, Al-Sabban E, et al. Clinical and epidemiological assessment of steroid-resistant nephrotic syndrome associated with the NPHS2 R229Q variant. Kidney Int. 2009;75(7):727–35.PubMedGoogle Scholar
  37. 37.
    Schwarz K, Simons M, Reiser J, Saleem MA, Faul C, Kriz W, et al. Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin. J Clin Invest. 2001;108(11):1621–9.PubMedCentralPubMedGoogle Scholar
  38. 38.
    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(1):131–9.PubMedCentralPubMedGoogle Scholar
  39. 39.
    Huber TB, Schermer B, Muller RU, Hohne M, Bartram M, Calixto A, et al. Podocin and MEC-2 bind cholesterol to regulate the activity of associated ion channels. Proc Natl Acad Sci U S A. 2006;103(46):17079–86.PubMedCentralPubMedGoogle Scholar
  40. 40.
    Huber TB, Simons M, Hartleben B, Sernetz L, Schmidts M, Gundlach E, et al. Molecular basis of the functional podocin-nephrin complex: mutations in the NPHS2 gene disrupt nephrin targeting to lipid raft microdomains. Hum Mol Genet. 2003;12(24):3397–405.PubMedGoogle Scholar
  41. 41.
    Huber TB, Kottgen M, Schilling B, Walz G, Benzing T. Interaction with podocin facilitates nephrin signaling. J Biol Chem. 2001;276(45):41543–6.PubMedGoogle Scholar
  42. 42.
    Huber TB, Schermer B, Benzing T. Podocin organizes ion channel-lipid supercomplexes: implications for mechanosensation at the slit diaphragm. Nephron Exp Nephrol. 2007;106(2):e27–31.PubMedGoogle Scholar
  43. 43.
    Reiser J, Polu KR, Moller CC, Kenlan P, Altintas MM, Wei C, et al. TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. Nat Genet. 2005;37(7):739–44.PubMedCentralPubMedGoogle Scholar
  44. 44.
    Sellin L, Huber TB, Gerke P, Quack I, Pavenstadt H, Walz G. NEPH1 defines a novel family of podocin interacting proteins. FASEB J. 2003;17(1):115–7.PubMedGoogle Scholar
  45. 45.
    Huber TB, Hartleben B, Kim J, Schmidts M, Schermer B, Keil A, et al. Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling. Mol Cell Biol. 2003;23(14):4917–28.PubMedCentralPubMedGoogle Scholar
  46. 46.
    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(2):400–5.PubMedGoogle Scholar
  47. 47.
    Niaudet P. Podocin and nephrotic syndrome: implications for the clinician. J Am Soc Nephrol. 2004;15(3):832–4.PubMedGoogle Scholar
  48. 48.
    Roselli S, Moutkine I, Gribouval O, Benmerah A, Antignac C. Plasma membrane targeting of podocin through the classical exocytic pathway: effect of NPHS2 mutations. Traffic (Copenhagen, Denmark). 2004;5(1):37–44.Google Scholar
  49. 49.
    Ohashi T, Uchida K, Uchida S, Sasaki S, Nihei H. Intracellular mislocalization of mutant podocin and correction by chemical chaperones. Histochem Cell Biol. 2003;119(3):257–64.PubMedGoogle Scholar
  50. 50.
    Frishberg Y, Feinstein S, Rinat C, Becker-Cohen R, Lerer I, Raas-Rothschild A, et al. The heart of children with steroid-resistant nephrotic syndrome: is it all podocin? J Am Soc Nephrol. 2006;17(1):227–31.PubMedGoogle Scholar
  51. 51.
    Caridi G, Dagnino M, Carrea A, Massella L, Amore A, Emma F, et al. Lack of cardiac anomalies in children with NPHS2 mutations. Nephrol Dial Transplant. 2007;22(5):1477–9.PubMedGoogle Scholar
  52. 52.
    Franceschini N, North KE, Kopp JB, McKenzie L, Winkler C. NPHS2 gene, nephrotic syndrome and focal segmental glomerulosclerosis: a HuGE review. Genet Med. 2006;8(2):63–75.PubMedGoogle Scholar
  53. 53.
    Pereira AC, Pereira AB, Mota GF, Cunha RS, Herkenhoff FL, Pollak MR, et al. NPHS2 R229Q functional variant is associated with microalbuminuria in the general population. Kidney Int. 2004;65(3):1026–30.PubMedGoogle Scholar
  54. 54.
    Kottgen A, Hsu CC, Coresh J, Shuldiner AR, Berthier-Schaad Y, Gambhir TR, et al. The association of podocin R229Q polymorphism with increased Albuminuria or reduced estimated GFR in a large population-based sample of US adults. Am J Kidney Dis. 2008;52(5):868–75.PubMedCentralPubMedGoogle Scholar
  55. 55.
    Tory K, Menyhard DK, 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(3):299–304.PubMedGoogle Scholar
  56. 56.
    Koziell A, Grech V, Hussain S, Lee G, Lenkkeri U, Tryggvason K, et al. Genotype/phenotype correlations of NPHS1 and NPHS2 mutations in nephrotic syndrome advocate a functional inter-relationship in glomerular filtration. Hum Mol Genet. 2002;11(4):379–88.PubMedGoogle Scholar
  57. 57.
    Schultheiss M, Ruf RG, Mucha BE, Wiggins R, Fuchshuber A, Lichtenberger A, et al. No evidence for genotype/phenotype correlation in NPHS1 and NPHS2 mutations. Pediatric Nephrology (Berlin, Germany). 2004;19(12):1340–8.Google Scholar
  58. 58.
    Jungraithmayr TC, Bulla M, Dippell J, Greiner C, Griebel M, Leichter HE, et al. Primary focal segmental glomerulosclerosis–long-term outcome after pediatric renal transplantation. Pediatr Transplant. 2005;9(2):226–31.PubMedGoogle Scholar
  59. 59.
    Tejani A, Stablein DH. Recurrence of focal segmental glomerulosclerosis posttransplantation: a special report of the North American Pediatric Renal Transplant Cooperative Study. J Am Soc Nephrol. 1992;2 Suppl 12:S258–63.PubMedGoogle Scholar
  60. 60.
    Weber S, Tonshoff B. Recurrence of focal-segmental glomerulosclerosis in children after renal transplantation: clinical and genetic aspects. Transplantation. 2005;80 Suppl 1:S128–34.PubMedGoogle Scholar
  61. 61.
    Carraro M, Caridi G, Bruschi M, Artero M, Bertelli R, Zennaro C, et al. Serum glomerular permeability activity in patients with podocin mutations (NPHS2) and steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2002;13(7):1946–52.PubMedGoogle Scholar
  62. 62.
    Becker-Cohen R, Bruschi M, Rinat C, Feinstein S, Zennaro C, Ghiggeri GM, et al. Recurrent nephrotic syndrome in homozygous truncating NPHS2 mutation is not due to anti-podocin antibodies. Am J Transplant. 2007;7(1):256–60.PubMedGoogle Scholar
  63. 63.
    Roselli S, Heidet L, Sich M, Henger A, Kretzler M, Gubler MC, et al. Early glomerular filtration defect and severe renal disease in podocin-deficient mice. Mol Cell Biol. 2004;24(2):550–60.PubMedCentralPubMedGoogle Scholar
  64. 64.
    Philippe A, Weber S, Esquivel EL, Houbron C, Hamard G, Ratelade J, et al. A missense mutation in podocin leads to early and severe renal disease in mice. Kidney Int. 2008;73(9):1038–47.PubMedGoogle Scholar
  65. 65.
    Ratelade J, Lavin TA, Muda AO, Morisset L, Mollet G, Boyer O, et al. Maternal environment interacts with modifier genes to influence progression of nephrotic syndrome. J Am Soc Nephrol. 2008;19(8):1491–9.PubMedCentralPubMedGoogle Scholar
  66. 66.
    Mollet G, Ratelade J, Boyer O, Muda AO, Morisset L, Lavin TA, et al. Podocin inactivation in mature kidneys causes focal segmental glomerulosclerosis and nephrotic syndrome. J Am Soc Nephrol. 2009;20(10):2181–9.PubMedCentralPubMedGoogle Scholar
  67. 67.
    Kramer-Zucker AG, Wiessner S, Jensen AM, Drummond IA. Organization of the pronephric filtration apparatus in zebrafish requires Nephrin, Podocin and the FERM domain protein Mosaic eyes. Dev Biol. 2005;285(2):316–29.PubMedCentralPubMedGoogle Scholar
  68. 68.
    Zhang F, Zhao Y, Han Z. An in vivo functional analysis system for renal gene discovery in Drosophila pericardial nephrocytes. J Am Soc Nephrol. 2013;24(2):191–7.PubMedCentralPubMedGoogle Scholar
  69. 69.
    Putaala H, Sainio K, Sariola H, Tryggvason K. Primary structure of mouse and rat nephrin cDNA and structure and expression of the mouse gene. J Am Soc Nephrol. 2000;11(6):991–1001.PubMedGoogle Scholar
  70. 70.
    Liu L, Done SC, Khoshnoodi J, Bertorello A, Wartiovaara J, Berggren PO, et al. Defective nephrin trafficking caused by missense mutations in the NPHS1 gene: insight into the mechanisms of congenital nephrotic syndrome. Hum Mol Genet. 2001;10(23):2637–44.PubMedGoogle Scholar
  71. 71.
    Liu XL, Done SC, Yan K, Kilpelainen P, Pikkarainen T, Tryggvason K. Defective trafficking of nephrin missense mutants rescued by a chemical chaperone. J Am Soc Nephrol. 2004;15(7):1731–8.PubMedGoogle Scholar
  72. 72.
    Kitamura A, Tsukaguchi H, Hiramoto R, Shono A, Doi T, Kagami S, et al. A familial childhood-onset relapsing nephrotic syndrome. Kidney Int. 2007;71(9):946–51.PubMedGoogle Scholar
  73. 73.
    Philippe A, Nevo F, Esquivel EL, Reklaityte D, Gribouval O, Tete MJ, et al. Nephrin mutations can cause childhood-onset steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2008;19(10):1871–8.PubMedCentralPubMedGoogle Scholar
  74. 74.
    Santin S, Garcia-Maset R, Ruiz P, Gimenez I, Zamora I, Pena A, et al. Nephrin mutations cause childhood- and adult-onset focal segmental glomerulosclerosis. Kidney Int. 2009;76(12):1268–76.PubMedGoogle Scholar
  75. 75.
    Wing MR, Bourdon DM, Harden TK. PLC-epsilon: a shared effector protein in Ras-, Rho-, and G alpha beta gamma-mediated signaling. Mol Interv. 2003;3(5):273–80.PubMedGoogle Scholar
  76. 76.
    Hinkes B, Wiggins RC, Gbadegesin R, Vlangos CN, Seelow D, Nurnberg G, et al. Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. Nat Genet. 2006;38(12):1397–405.PubMedGoogle Scholar
  77. 77.
    Lehtonen S, Ryan JJ, Kudlicka K, Iino N, Zhou H, Farquhar MG. Cell junction-associated proteins IQGAP1, MAGI-2, CASK, spectrins, and alpha-actinin are components of the nephrin multiprotein complex. Proc Natl Acad Sci U S A. 2005;102(28):9814–9.PubMedCentralPubMedGoogle Scholar
  78. 78.
    Gbadegesin R, Hinkes BG, Hoskins BE, Vlangos CN, Heeringa SF, Liu J, et al. Mutations in PLCE1 are a major cause of isolated diffuse mesangial sclerosis (IDMS). Nephrol Dial Transplant. 2008;23(4):1291–7.PubMedGoogle Scholar
  79. 79.
    Boyer O, Benoit G, Gribouval O, Nevo F, Pawtowski A, Bilge I, et al. Mutational analysis of the PLCE1 gene in steroid resistant nephrotic syndrome. J Med Genet. 2010;47(7):445–52.PubMedGoogle Scholar
  80. 80.
    Quaggin SE. A new piece in the nephrotic puzzle. Nat Genet. 2006;38(12):1360–1.PubMedGoogle Scholar
  81. 81.
    Gilbert RD, Turner CL, Gibson J, Bass PS, Haq MR, Cross E, et al. Mutations in phospholipase C epsilon 1 are not sufficient to cause diffuse mesangial sclerosis. Kidney Int. 2009;75(4):415–9.PubMedGoogle Scholar
  82. 82.
    Riazuddin S, Castelein CM, Ahmed ZM, Lalwani AK, Mastroianni MA, Naz S, et al. Dominant modifier DFNM1 suppresses recessive deafness DFNB26. Nat Genet. 2000;26(4):431–4.PubMedGoogle Scholar
  83. 83.
    Katsanis N, Ansley SJ, Badano JL, Eichers ER, Lewis RA, Hoskins BE, et al. Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder. Science. 2001;293(5538):2256–9.PubMedGoogle Scholar
  84. 84.
    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(4):295–306.PubMedCentralPubMedGoogle Scholar
  85. 85.
    Sanna-Cherchi S, Burgess KE, Nees SN, Caridi G, Weng PL, 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(4):389–96.PubMedGoogle Scholar
  86. 86.
    Al-Hamed MH, Al-Sabban E, Al-Mojalli H, Al-Harbi N, Faqeih E, Al Shaya H, et al. A molecular genetic analysis of childhood nephrotic syndrome in a cohort of Saudi Arabian families. J Hum Genet. 2013;58(7):480–9.PubMedGoogle Scholar
  87. 87.
    Mao J, Wang D, Mataleena P, He B, Niu D, Katayama K, et al. Myo1e impairment results in actin reorganization, podocyte dysfunction, and proteinuria in zebrafish and cultured podocytes. PLoS One. 2013;8(8):e72750.PubMedCentralPubMedGoogle Scholar
  88. 88.
    Krendel M, Kim SV, Willinger T, Wang T, Kashgarian M, Flavell RA, et al. Disruption of Myosin 1e promotes podocyte injury. J Am Soc Nephrol. 2009;20(1):86–94.PubMedCentralPubMedGoogle Scholar
  89. 89.
    Chase SE, Encina CV, Stolzenburg LR, Tatum AH, Holzman LB, Krendel M. Podocyte-specific knockout of myosin 1e disrupts glomerular filtration. Am J Physiol Renal Physiol. 2012;303(7):F1099–106.PubMedCentralPubMedGoogle Scholar
  90. 90.
    Thomas PE, Wharram BL, Goyal M, Wiggins JE, Holzman LB, Wiggins RC. GLEPP1, a renal glomerular epithelial cell (podocyte) membrane protein-tyrosine phosphatase. Identification, molecular cloning, and characterization in rabbit. J Biol Chem. 1994;269(31):19953–62.PubMedGoogle Scholar
  91. 91.
    Wharram BL, Goyal M, Gillespie PJ, Wiggins JE, Kershaw DB, Holzman LB, et al. Altered podocyte structure in GLEPP1 (Ptpro)-deficient mice associated with hypertension and low glomerular filtration rate. J Clin Invest. 2000;106(10):1281–90.PubMedCentralPubMedGoogle Scholar
  92. 92.
    Ozaltin F, Ibsirlioglu T, Taskiran EZ, Baydar DE, Kaymaz F, Buyukcelik M, et al. Disruption of PTPRO causes childhood-onset nephrotic syndrome. Am J Hum Genet. 2011;89(1):139–47.PubMedCentralPubMedGoogle Scholar
  93. 93.
    Ebarasi L, Ashraf S, Bierzynska A, Gee HY, McCarthy HJ, Lovric S, et al. Defects of CRB2 cause steroid-resistant nephrotic syndrome. Am J Hum Genet. 2015;96(1):153–61.PubMedGoogle Scholar
  94. 94.
    Xiao Z, Patrakka J, Nukui M, Chi L, Niu D, Betsholtz C, et al. Deficiency in Crumbs homolog 2 (Crb2) affects gastrulation and results in embryonic lethality in mice. Dev Dyn. 2011;240(12):2646–56.PubMedGoogle Scholar
  95. 95.
    Slavotinek A, Kaylor J, Pierce H, Cahr M, DeWard SJ, 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(1):162–9.PubMedGoogle Scholar
  96. 96.
    Dustin ML, Olszowy MW, Holdorf AD, Li J, Bromley S, Desai N, et al. A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts. Cell. 1998;94(5):667–77.PubMedGoogle Scholar
  97. 97.
    Shih NY, Li J, Karpitskii V, Nguyen A, Dustin ML, Kanagawa O, et al. Congenital nephrotic syndrome in mice lacking CD2-associated protein. Science. 1999;286(5438):312–5.PubMedGoogle Scholar
  98. 98.
    Lehtonen S, Zhao F, Lehtonen E. CD2-associated protein directly interacts with the actin cytoskeleton. Am J Physiol Renal Physiol. 2002;283(4):F734–43.PubMedGoogle Scholar
  99. 99.
    Grunkemeyer JA, Kwoh C, Huber TB, Shaw AS. CD2-associated protein (CD2AP) expression in podocytes rescues lethality of CD2AP deficiency. J Biol Chem. 2005;280(33):29677–81.PubMedGoogle Scholar
  100. 100.
    Kim JM, Wu H, Green G, Winkler CA, Kopp JB, Miner JH, et al. CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility. Science. 2003;300(5623):1298–300.PubMedGoogle Scholar
  101. 101.
    Lowik MM, Groenen PJ, Pronk I, Lilien MR, Goldschmeding R, Dijkman HB, et al. Focal segmental glomerulosclerosis in a patient homozygous for a CD2AP mutation. Kidney Int. 2007;72(10):1198–203.PubMedGoogle Scholar
  102. 102.
    Davis EE, Zhang Q, Liu Q, Diplas BH, Davey LM, Hartley J, et al. TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum. Nat Genet. 2011;43(3):189–96.PubMedCentralPubMedGoogle Scholar
  103. 103.
    Mathis BJ, Calabrese KE, Slick GL. Familial glomerular disease with asymptomatic proteinuria and nephrotic syndrome: a new clinical entity. J Am Osteopath Assoc. 1992;92(7):875–80. 7.PubMedGoogle Scholar
  104. 104.
    Mathis BJ, Kim SH, Calabrese K, Haas M, Seidman JG, Seidman CE, et al. A locus for inherited focal segmental glomerulosclerosis maps to chromosome 19q13. Kidney Int. 1998;53(2):282–6.PubMedGoogle Scholar
  105. 105.
    Kaplan JM, Kim SH, North KN, Rennke H, Correia LA, Tong HQ, et al. Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. Nat Genet. 2000;24(3):251–6.PubMedGoogle Scholar
  106. 106.
    Ichimura K, Kurihara H, Sakai T. Actin filament organization of foot processes in rat podocytes. J Histochem Cytochem. 2003;51(12):1589–600.PubMedGoogle Scholar
  107. 107.
    Weins A, Kenlan P, Herbert S, Le TC, Villegas I, Kaplan BS, et al. Mutational and biological analysis of alpha-actinin-4 in focal segmental glomerulosclerosis. J Am Soc Nephrol. 2005;16(12):3694–701.PubMedGoogle Scholar
  108. 108.
    Yao J, Le TC, Kos CH, Henderson JM, Allen PG, Denker BM, et al. Alpha-actinin-4-mediated FSGS: an inherited kidney disease caused by an aggregated and rapidly degraded cytoskeletal protein. PLoS Biol. 2004;2(6):e167.PubMedCentralPubMedGoogle Scholar
  109. 109.
    Michaud JL, Lemieux LI, Dube M, Vanderhyden BC, Robertson SJ, Kennedy CR. Focal and segmental glomerulosclerosis in mice with podocyte-specific expression of mutant alpha-actinin-4. J Am Soc Nephrol. 2003;14(5):1200–11.PubMedGoogle Scholar
  110. 110.
    Michaud JL, Chaisson KM, Parks RJ, Kennedy CR. FSGS-associated alpha-actinin-4 (K256E) impairs cytoskeletal dynamics in podocytes. Kidney Int. 2006;70(6):1054–61.PubMedGoogle Scholar
  111. 111.
    Pollak MR, Alexander MP, Henderson JM. A case of familial kidney disease. Clin J Am Soc Nephrol. 2007;2(6):1367–74.PubMedGoogle Scholar
  112. 112.
    Choi HJ, Lee BH, Cho HY, Moon KC, Ha IS, Nagata M, et al. Familial focal segmental glomerulosclerosis associated with an ACTN4 mutation and paternal germline mosaicism. Am J Kidney Dis. 2008;51(5):834–8.PubMedGoogle Scholar
  113. 113.
    Barua M, Brown EJ, Charoonratana VT, Genovese G, Sun H, Pollak MR. Mutations in the INF2 gene account for a significant proportion of familial but not sporadic focal and segmental glomerulosclerosis. Kidney Int. 2013;83(2):316–22.PubMedCentralPubMedGoogle Scholar
  114. 114.
    Winn MP, Conlon PJ, Lynn KL, Howell DN, Slotterbeck BD, Smith AH, et al. Linkage of a gene causing familial focal segmental glomerulosclerosis to chromosome 11 and further evidence of genetic heterogeneity. Genomics. 1999;58(2):113–20.PubMedGoogle Scholar
  115. 115.
    Winn MP, Conlon PJ, Lynn KL, Farrington MK, Creazzo T, Hawkins AF, et al. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science. 2005;308(5729):1801–4.PubMedGoogle Scholar
  116. 116.
    Heeringa SF, Moller CC, Du J, Yue L, Hinkes B, Chernin G, et al. A novel TRPC6 mutation that causes childhood FSGS. PLoS One. 2009;4(11):e7771.PubMedCentralPubMedGoogle Scholar
  117. 117.
    Santin S, Ars E, Rossetti S, Salido E, Silva I, Garcia-Maset R, et al. TRPC6 mutational analysis in a large cohort of patients with focal segmental glomerulosclerosis. Nephrol Dial Transplant. 2009;24(10):3089–96.PubMedGoogle Scholar
  118. 118.
    Gigante M, Caridi G, Montemurno E, Soccio M, D’Apolito M, Cerullo G, et al. TRPC6 mutations in children with steroid-resistant nephrotic syndrome and atypical phenotype. Clin J Am Soc Nephrol. 2011;6(7):1626–34.PubMedGoogle Scholar
  119. 119.
    Lion M, Boyer O, Niaudet P, Charbit M, Eckart P, Nevo F, et al. Mutation de TRPC6: a rare cause of steroid-resistant nephrotic syndrome in children. Pediatr Nephrol. 2012;27:1702.Google Scholar
  120. 120.
    Nilius B, Owsianik G, Voets T, Peters JA. Transient receptor potential cation channels in disease. Physiol Rev. 2007;87(1):165–217.PubMedGoogle Scholar
  121. 121.
    Spassova MA, Hewavitharana T, Xu W, Soboloff J, Gill DL. A common mechanism underlies stretch activation and receptor activation of TRPC6 channels. Proc Natl Acad Sci U S A. 2006;103(44):16586–91.PubMedCentralPubMedGoogle Scholar
  122. 122.
    Brown EJ, Schlondorff JS, Becker DJ, Tsukaguchi H, Tonna SJ, Uscinski AL, et al. Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis. Nat Genet. 2010;42(1):72–6.PubMedCentralPubMedGoogle Scholar
  123. 123.
    Boyer O, Benoit G, Gribouval O, Nevo F, Tete MJ, Dantal J, et al. Mutations in INF2 are a major cause of autosomal dominant focal segmental glomerulosclerosis. J Am Soc Nephrol. 2011;22(2):239–45.PubMedCentralPubMedGoogle Scholar
  124. 124.
    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(25):2377–88.PubMedGoogle Scholar
  125. 125.
    Chesarone MA, DuPage AG, Goode BL. Unleashing formins to remodel the actin and microtubule cytoskeletons. Nat Rev Mol Cell Biol. 2010;11(1):62–74.PubMedGoogle Scholar
  126. 126.
    Akilesh S, Suleiman H, Yu H, Stander MC, 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(10):4127–37.PubMedCentralPubMedGoogle Scholar
  127. 127.
    Gbadegesin RA, 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(9):1991–2002.PubMedGoogle Scholar
  128. 128.
    Dreyer SD, Zhou G, Baldini A, Winterpacht A, Zabel B, Cole W, et al. Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome. Nat Genet. 1998;19(1):47–50.PubMedGoogle Scholar
  129. 129.
    Boyer O, Woerner S, Yang F, Oakeley EJ, Linghu B, Gribouval O, et al. LMX1B mutations cause hereditary FSGS without extrarenal involvement. J Am Soc Nephrol. 2013;24(8):1216–22.PubMedCentralPubMedGoogle Scholar
  130. 130.
    Edwards N, Rice SJ, Raman S, Hynes AM, Srivastava S, Moore I, et al. A novel LMX1B mutation in a family with end-stage renal disease of ‘unknown cause’. Clin Kidney J. 2015;8(1):113–9.PubMedCentralPubMedGoogle Scholar
  131. 131.
    Malone AF, Phelan PJ, Hall G, Cetincelik U, Homstad A, Alonso AS, et al. Rare hereditary COL4A3/COL4A4 variants may be mistaken for familial focal segmental glomerulosclerosis. Kidney Int. 2014;86(6):1253–9.PubMedCentralPubMedGoogle Scholar
  132. 132.
    Moriniere V, Dahan K, Hilbert P, Lison M, Lebbah S, Topa A, et al. Improving mutation screening in familial hematuric nephropathies through next generation sequencing. J Am Soc Nephrol. 2014;25(12):2740–51.PubMedGoogle Scholar
  133. 133.
    Xie J, Wu X, Ren H, Wang W, Wang Z, Pan X, et al. COL4A3 mutations cause focal segmental glomerulosclerosis. J Mol Cell Biol. 2014;6(6):498–505.PubMedGoogle Scholar
  134. 134.
    Lin F, Bian F, Zou J, Wu X, Shan J, Lu W, et al. Whole exome sequencing reveals novel COL4A3 and COL4A4 mutations and resolves diagnosis in Chinese families with kidney disease. BMC Nephrol. 2014;15:175.PubMedCentralPubMedGoogle Scholar
  135. 135.
    Pritchard-Jones K, Fleming S, Davidson D, Bickmore W, Porteous D, Gosden C, et al. The candidate Wilms’ tumour gene is involved in genitourinary development. Nature. 1990;346(6280):194–7.PubMedGoogle Scholar
  136. 136.
    Rivera MN, Haber DA. Wilms’ tumour: connecting tumorigenesis and organ development in the kidney. Nat Rev Cancer. 2005;5(9):699–712.PubMedGoogle Scholar
  137. 137.
    Morrison AA, Viney RL, Saleem MA, Ladomery MR. New insights into the function of the Wilms tumor suppressor gene WT1 in podocytes. Am J Physiol Renal Physiol. 2008;295(1):F12–7.PubMedGoogle Scholar
  138. 138.
    Niaudet P, Gubler MC. WT1 and glomerular diseases. Pediatr Nephrol. 2006;21(11):1653–60.PubMedGoogle Scholar
  139. 139.
    Jeanpierre C, Denamur E, Henry I, Cabanis MO, Luce S, Cecille A, et al. Identification of constitutional WT1 mutations, in patients with isolated diffuse mesangial sclerosis, and analysis of genotype/phenotype correlations by use of a computerized mutation database. Am J Hum Genet. 1998;62(4):824–33.PubMedCentralPubMedGoogle Scholar
  140. 140.
    Klamt B, Koziell A, Poulat F, Wieacker P, Scambler P, Berta P, et al. Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/−KTS splice isoforms. Hum Mol Genet. 1998;7(4):709–14.PubMedGoogle Scholar
  141. 141.
    Hall G, Gbadegesin RA, Lavin P, Wu G, Liu Y, Oh EC, et al. A novel missense mutation of Wilms’ Tumor 1 causes autosomal dominant FSGS. J Am Soc Nephrol. 2014;26(4):831–43.PubMedGoogle Scholar
  142. 142.
    Benetti E, Caridi G, Malaventura C, Dagnino M, Leonardi E, Artifoni L, et al. A novel WT1 gene mutation in a three-generation family with progressive isolated focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2010;5(4):698–702.PubMedCentralPubMedGoogle Scholar
  143. 143.
    Guaragna MS, Lutaif AC, Piveta CS, Belangero VM, Maciel-Guerra AT, Guerra Jr G, et al. Two distinct WT1 mutations identified in patients and relatives with isolated nephrotic proteinuria. Biochem Biophys Res Commun. 2013;441(2):371–6.PubMedGoogle Scholar
  144. 144.
    Zhu C, Zhao F, Zhang W, Wu H, Chen Y, Ding G, et al. A familial WT1 mutation associated with incomplete Denys-Drash syndrome. Eur J Pediatr. 2013;172(10):1357–62.PubMedGoogle Scholar
  145. 145.
    Coppes MJ, Liefers GJ, Higuchi M, Zinn AB, Balfe JW, Williams BR. Inherited WT1 mutation in Denys-Drash syndrome. Cancer Res. 1992;52(21):6125–8.PubMedGoogle Scholar
  146. 146.
    Gessler M, Poustka A, Cavenee W, Neve RL, Orkin SH, Bruns GA. Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. Nature. 1990;343(6260):774–8.PubMedGoogle Scholar
  147. 147.
    Kreidberg JA, Sariola H, Loring JM, Maeda M, Pelletier J, Housman D, et al. WT-1 is required for early kidney development. Cell. 1993;74(4):679–91.PubMedGoogle Scholar
  148. 148.
    Moore AW, Schedl A, McInnes L, Doyle M, Hecksher-Sorensen J, Hastie ND. YAC transgenic analysis reveals Wilms’ tumour 1 gene activity in the proliferating coelomic epithelium, developing diaphragm and limb. Mech Dev. 1998;79(1–2):169–84.PubMedGoogle Scholar
  149. 149.
    Davies JA, Ladomery M, Hohenstein P, Michael L, Shafe A, Spraggon L, et al. Development of an siRNA-based method for repressing specific genes in renal organ culture and its use to show that the Wt1 tumour suppressor is required for nephron differentiation. Hum Mol Genet. 2004;13(2):235–46.PubMedGoogle Scholar
  150. 150.
    Denys P, Malvaux P, Van Den Berghe H, Tanghe W, Proesmans W. Association of an anatomo-pathological syndrome of male pseudohermaphroditism, Wilms’ tumor, parenchymatous nephropathy and XX/XY mosaicism. Arch Fr Pediatr. 1967;24(7):729–39.PubMedGoogle Scholar
  151. 151.
    Drash A, Sherman F, Hartmann WH, Blizzard RM. A syndrome of pseudohermaphroditism, Wilms’ tumor, hypertension, and degenerative renal disease. J Pediatr. 1970;76(4):585–93.PubMedGoogle Scholar
  152. 152.
    Habib R, Loirat C, Gubler MC, Niaudet P, Bensman A, Levy M, et al. The nephropathy associated with male pseudohermaphroditism and Wilms’ tumor (Drash syndrome): a distinctive glomerular lesion–report of 10 cases. Clin Nephrol. 1985;24(6):269–78.PubMedGoogle Scholar
  153. 153.
    Hastie ND. Dominant negative mutations in the Wilms tumour (WT1) gene cause Denys-Drash syndrome–proof that a tumour-suppressor gene plays a crucial role in normal genitourinary development. Hum Mol Genet. 1992;1(5):293–5.PubMedGoogle Scholar
  154. 154.
    Pelletier J, Bruening W, Kashtan CE, Mauer SM, Manivel JC, Striegel JE, et al. Germline mutations in the Wilms’ tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell. 1991;67(2):437–47.PubMedGoogle Scholar
  155. 155.
    Lipska BS, Ranchin B, Iatropoulos P, Gellermann J, Melk A, Ozaltin F, et al. Genotype-phenotype associations in WT1 glomerulopathy. Kidney Int. 2014;85(5):1169–78.PubMedGoogle Scholar
  156. 156.
    Little M, Wells C. A clinical overview of WT1 gene mutations. Hum Mutat. 1997;9(3):209–25.PubMedGoogle Scholar
  157. 157.
    Ito S, Takata A, Hataya H, Ikeda M, Kikuchi H, Hata J, et al. Isolated diffuse mesangial sclerosis and Wilms tumor suppressor gene. J Pediatr. 2001;138(3):425–7.PubMedGoogle Scholar
  158. 158.
    Moorthy AV, Chesney RW, Lubinsky M. Chronic renal failure and XY gonadal dysgenesis: “Frasier” syndrome–a commentary on reported cases. Am J Med Genet Suppl. 1987;3:297–302.PubMedGoogle Scholar
  159. 159.
    Haber DA, Sohn RL, Buckler AJ, Pelletier J, Call KM, Housman DE. Alternative splicing and genomic structure of the Wilms tumor gene WT1. Proc Natl Acad Sci U S A. 1991;88(21):9618–22.PubMedCentralPubMedGoogle Scholar
  160. 160.
    Hammes A, Guo JK, Lutsch G, Leheste JR, Landrock D, Ziegler U, et al. Two splice variants of the Wilms’ tumor 1 gene have distinct functions during sex determination and nephron formation. Cell. 2001;106(3):319–29.PubMedGoogle Scholar
  161. 161.
    Barbaux S, Niaudet P, Gubler MC, Grunfeld JP, Jaubert F, Kuttenn F, et al. Donor splice-site mutations in WT1 are responsible for Frasier syndrome. Nat Genet. 1997;17(4):467–70.PubMedGoogle Scholar
  162. 162.
    Miller RW, Fraumeni Jr JF, Manning MD. Association of Wilms’s tumor with Aniridia, hemihypertrophy and other congenital malformations. N Engl J Med. 1964;270:922–7.PubMedGoogle Scholar
  163. 163.
    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(10):2215–8.PubMedGoogle Scholar
  164. 164.
    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(10):2219–23.PubMedGoogle Scholar
  165. 165.
    Mucha B, Ozaltin F, Hinkes BG, Hasselbacher K, Ruf RG, Schultheiss M, et al. Mutations in the Wilms’ tumor 1 gene cause isolated steroid resistant nephrotic syndrome and occur in exons 8 and 9. Pediatr Res. 2006;59(2):325–31.PubMedGoogle Scholar
  166. 166.
    Zenker M, Tralau T, Lennert T, Pitz S, Mark K, Madlon H, et al. Congenital nephrosis, mesangial sclerosis, and distinct eye abnormalities with microcoria: an autosomal recessive syndrome. Am J Med Genet. 2004;130(2):138–45.Google Scholar
  167. 167.
    Pierson M, Cordier J, Hervouuet F, Rauber G. [An unusual congenital and familial congenital malformative combination involving the eye and kidney]. J Genet Hum. 1963;12:184–213.PubMedGoogle Scholar
  168. 168.
    Zenker M, Aigner T, Wendler O, Tralau T, Muntefering H, Fenski R, et al. Human laminin beta2 deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities. Hum Mol Genet. 2004;13(21):2625–32.PubMedGoogle Scholar
  169. 169.
    Noakes PG, Miner JH, Gautam M, Cunningham JM, Sanes JR, Merlie JP. The renal glomerulus of mice lacking s-laminin/laminin beta 2: nephrosis despite molecular compensation by laminin beta 1. Nat Genet. 1995;10(4):400–6.PubMedGoogle Scholar
  170. 170.
    Hasselbacher K, Wiggins RC, Matejas V, Hinkes BG, Mucha B, Hoskins BE, et al. Recessive missense mutations in LAMB2 expand the clinical spectrum of LAMB2-associated disorders. Kidney Int. 2006;70(6):1008–12.PubMedGoogle Scholar
  171. 171.
    Choi HJ, Lee BH, Kang JH, Jeong HJ, Moon KC, Ha IS, et al. Variable phenotype of Pierson syndrome. Pediatr Nephrol (Berlin Germany). 2008;23(6):995–1000.Google Scholar
  172. 172.
    Kagan M, Cohen AH, Matejas V, Vlangos C, Zenker M. A milder variant of Pierson syndrome. Pediatr Nephrol (Berlin Germany). 2008;23(2):323–7.Google Scholar
  173. 173.
    Matejas V, Al-Gazali L, Amirlak I, Zenker M. A syndrome comprising childhood-onset glomerular kidney disease and ocular abnormalities with progressive loss of vision is caused by mutated LAMB2. Nephrol Dial Transplant. 2006;21(11):3283–6.PubMedGoogle Scholar
  174. 174.
    Matejas V, Hinkes B, Alkandari F, Al-Gazali L, Annexstad E, Aytac MB, et al. Mutations in the human laminin beta2 (LAMB2) gene and the associated phenotypic spectrum. Hum Mutat. 2010;31(9):992–1002.PubMedCentralPubMedGoogle Scholar
  175. 175.
    Sasaki T, Fassler R, Hohenester E. Laminin: the crux of basement membrane assembly. J Cell Biol. 2004;164(7):959–63.PubMedCentralPubMedGoogle Scholar
  176. 176.
    Jarad G, Cunningham J, Shaw AS, Miner JH. Proteinuria precedes podocyte abnormalities inLamb2−/− mice, implicating the glomerular basement membrane as an albumin barrier. J Clin Invest. 2006;116(8):2272–9.PubMedCentralPubMedGoogle Scholar
  177. 177.
    Chen YM, Kikkawa Y, Miner JH. A missense LAMB2 mutation causes congenital nephrotic syndrome by impairing laminin secretion. J Am Soc Nephrol. 2011;22(5):849–58.PubMedCentralPubMedGoogle Scholar
  178. 178.
    Suh JH, Jarad G, VanDeVoorde RG, Miner JH. Forced expression of laminin beta1 in podocytes prevents nephrotic syndrome in mice lacking laminin beta2, a model for Pierson syndrome. Proc Natl Acad Sci U S A. 2011;108(37):15348–53.PubMedCentralPubMedGoogle Scholar
  179. 179.
    Guidera KJ, Satterwhite Y, Ogden JA, Pugh L, Ganey T. Nail patella syndrome: a review of 44 orthopaedic patients. J Pediatr Orthop. 1991;11(6):737–42.PubMedGoogle Scholar
  180. 180.
    Bennett WM, Musgrave JE, Campbell RA, Elliot D, Cox R, Brooks RE, et al. The nephropathy of the nail-patella syndrome. Clinicopathologic analysis of 11 kindred. Am J Med. 1973;54(3):304–19.PubMedGoogle Scholar
  181. 181.
    Looij Jr BJ, te Slaa RL, Hogewind BL, van de Kamp JJ. Genetic counselling in hereditary osteo-onychodysplasia (HOOD, nail-patella syndrome) with nephropathy. J Med Genet. 1988;25(10):682–6.PubMedCentralPubMedGoogle Scholar
  182. 182.
    McIntosh I, Dreyer SD, Clough MV, Dunston JA, Eyaid W, Roig CM, et al. Mutation analysis of LMX1B gene in nail-patella syndrome patients. Am J Hum Genet. 1998;63(6):1651–8.PubMedCentralPubMedGoogle Scholar
  183. 183.
    Knoers NV, Bongers EM, van Beersum SE, Lommen EJ, van Bokhoven H, Hol FA. Nail-patella syndrome: identification of mutations in the LMX1B gene in Dutch families. J Am Soc Nephrol. 2000;11(9):1762–6.PubMedGoogle Scholar
  184. 184.
    Bongers EM, Huysmans FT, Levtchenko E, de Rooy JW, Blickman JG, Admiraal RJ, et al. Genotype-phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy. Eur J Hum Genet. 2005;13(8):935–46.PubMedGoogle Scholar
  185. 185.
    Sweeney E, Fryer A, Mountford R, Green A, McIntosh I. Nail patella syndrome: a review of the phenotype aided by developmental biology. J Med Genet. 2003;40(3):153–62.PubMedCentralPubMedGoogle Scholar
  186. 186.
    Gubler MC. Inherited diseases of the glomerular basement membrane. Nat Clin Pract Nephrol. 2008;4(1):24–37.PubMedGoogle Scholar
  187. 187.
    Ben-Bassat M, Cohen L, Rosenfeld J. The glomerular basement membrane in the nail-patella syndrome. Arch Pathol. 1971;92(5):350–5.PubMedGoogle Scholar
  188. 188.
    Hoyer JR, Michael AF, Vernier RL. Renal disease in nail-patella syndrome: clinical and morphologic studies. Kidney Int. 1972;2(4):231–8.PubMedGoogle Scholar
  189. 189.
    Gubler MC, Levy M, Naizot C, Habib R. Glomerular basement membrane changes in hereditary glomerular diseases. Ren Physiol. 1980;3(1–6):405–13.PubMedGoogle Scholar
  190. 190.
    Lichter PR, Richards JE, Downs CA, Stringham HM, Boehnke M, Farley FA. Cosegregation of open-angle glaucoma and the nail-patella syndrome. Am J Ophthalmol. 1997;124(4):506–15.PubMedGoogle Scholar
  191. 191.
    Vollrath D, Jaramillo-Babb VL, Clough MV, McIntosh I, Scott KM, Lichter PR, et al. Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome. Hum Mol Genet. 1998;7(7):1091–8.PubMedGoogle Scholar
  192. 192.
    Hamlington JD, Jones C, McIntosh I. Twenty-two novel LMX1B mutations identified in nail patella syndrome (NPS) patients. Hum Mutat. 2001;18(5):458.PubMedGoogle Scholar
  193. 193.
    Bongers EM, de Wijs IJ, Marcelis C, Hoefsloot LH, Knoers NV. Identification of entire LMX1B gene deletions in nail patella syndrome: evidence for haploinsufficiency as the main pathogenic mechanism underlying dominant inheritance in man. Eur J Hum Genet. 2008;16(10):1240–4.PubMedGoogle Scholar
  194. 194.
    Chen H, Lun Y, Ovchinnikov D, Kokubo H, Oberg KC, Pepicelli CV, et al. Limb and kidney defects in Lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome. Nat Genet. 1998;19(1):51–5.PubMedGoogle Scholar
  195. 195.
    Morello R, Zhou G, Dreyer SD, Harvey SJ, Ninomiya Y, Thorner PS, et al. Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome. Nat Genet. 2001;27(2):205–8.PubMedGoogle Scholar
  196. 196.
    Miner JH, Morello R, Andrews KL, Li C, Antignac C, Shaw AS, et al. Transcriptional induction of slit diaphragm genes by Lmx1b is required in podocyte differentiation. J Clin Invest. 2002;109(8):1065–72.PubMedCentralPubMedGoogle Scholar
  197. 197.
    Rohr C, Prestel J, Heidet L, Hosser H, Kriz W, Johnson RL, et al. The LIM-homeodomain transcription factor Lmx1b plays a crucial role in podocytes. J Clin Invest. 2002;109(8):1073–82.PubMedCentralPubMedGoogle Scholar
  198. 198.
    Heidet L, Bongers EM, Sich M, Zhang SY, Loirat C, Meyrier A, et al. In vivo expression of putative LMX1B targets in nail-patella syndrome kidneys. Am J Pathol. 2003;163(1):145–55.PubMedCentralPubMedGoogle Scholar
  199. 199.
    Schimke RN, Horton WA, King CR. Chondroitin-6-sulphaturia, defective cellular immunity, and nephrotic syndrome. Lancet. 1971;2(7733):1088–9.PubMedGoogle Scholar
  200. 200.
    Saraiva JM, Dinis A, Resende C, Faria E, Gomes C, Correia AJ, et al. Schimke immuno-osseous dysplasia: case report and review of 25 patients. J Med Genet. 1999;36(10):786–9.PubMedCentralPubMedGoogle Scholar
  201. 201.
    Boerkoel CF, O’Neill S, Andre JL, Benke PJ, Bogdanovic R, Bulla M, et al. Manifestations and treatment of Schimke immuno-osseous dysplasia: 14 new cases and a review of the literature. Eur J Pediatr. 2000;159(1–2):1–7.PubMedGoogle Scholar
  202. 202.
    Clewing JM, Antalfy BC, Lucke T, Najafian B, Marwedel KM, Hori A, et al. Schimke immuno-osseous dysplasia: a clinicopathological correlation. J Med Genet. 2007;44(2):122–30.PubMedCentralPubMedGoogle Scholar
  203. 203.
    Lucke T, Clewing JM, Boerkoel CF, Hartmann H, Das AM, Knauth M, et al. Cerebellar atrophy in Schimke-immuno-osseous dysplasia. Am J Med Genet. 2007;143A(17):2040–5.PubMedGoogle Scholar
  204. 204.
    Boerkoel CF, Takashima H, John J, Yan J, Stankiewicz P, Rosenbarker L, et al. Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia. Nat Genet. 2002;30(2):215–20.PubMedGoogle Scholar
  205. 205.
    Clewing JM, Fryssira H, Goodman D, Smithson SF, Sloan EA, Lou S, et al. Schimke immunoosseous dysplasia: suggestions of genetic diversity. Hum Mutat. 2007;28(3):273–83.PubMedGoogle Scholar
  206. 206.
    DiMauro S, Moraes CT. Mitochondrial encephalomyopathies. Arch Neurol. 1993;50(11):1197–208.PubMedGoogle Scholar
  207. 207.
    Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, et al. Sequence and organization of the human mitochondrial genome. Nature. 1981;290(5806):457–65.PubMedGoogle Scholar
  208. 208.
    Goto Y, Nonaka I, Horai S. A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature. 1990;348(6302):651–3.PubMedGoogle Scholar
  209. 209.
    van den Ouweland JM, Lemkes HH, Ruitenbeek W, Sandkuijl LA, de Vijlder MF, Struyvenberg PA, et al. Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nat Genet. 1992;1(5):368–71.PubMedGoogle Scholar
  210. 210.
    Chinnery PF, Turnbull DM. Mitochondrial DNA and disease. Lancet. 1999;354 Suppl 1:SI17–21.PubMedGoogle Scholar
  211. 211.
    Yoshida R, Ishida Y, Hozumi T, Ueno H, Kishimoto M, Kasuga M, et al. Congestive heart failure in mitochondrial diabetes mellitus. Lancet. 1994;344(8933):1375.PubMedGoogle Scholar
  212. 212.
    Jansen JJ, Maassen JA, van der Woude FJ, Lemmink HA, van den Ouweland JM, t’ Hart LM, et al. Mutation in mitochondrial tRNA(Leu(UUR)) gene associated with progressive kidney disease. J Am Soc Nephrol. 1997;8(7):1118–24.PubMedGoogle Scholar
  213. 213.
    Kurogouchi F, Oguchi T, Mawatari E, Yamaura S, Hora K, Takei M, et al. A case of mitochondrial cytopathy with a typical point mutation for MELAS, presenting with severe focal-segmental glomerulosclerosis as main clinical manifestation. Am J Nephrol. 1998;18(6):551–6.PubMedGoogle Scholar
  214. 214.
    Nakamura S, Yoshinari M, Doi Y, Yoshizumi H, Katafuchi R, Yokomizo Y, et al. Renal complications in patients with diabetes mellitus associated with an A to G mutation of mitochondrial DNA at the 3243 position of leucine tRNA. Diabetes Res Clin Pract. 1999;44(3):183–9.PubMedGoogle Scholar
  215. 215.
    Doleris LM, Hill GS, Chedin P, Nochy D, Bellanne-Chantelot C, Hanslik T, et al. Focal segmental glomerulosclerosis associated with mitochondrial cytopathy. Kidney Int. 2000;58(5):1851–8.PubMedGoogle Scholar
  216. 216.
    Hotta O, Inoue CN, Miyabayashi S, Furuta T, Takeuchi A, Taguma Y. Clinical and pathologic features of focal segmental glomerulosclerosis with mitochondrial tRNALeu(UUR) gene mutation. Kidney Int. 2001;59(4):1236–43.PubMedGoogle Scholar
  217. 217.
    Hirano M, Konishi K, Arata N, Iyori M, Saruta T, Kuramochi S, et al. Renal complications in a patient with A-to-G mutation of mitochondrial DNA at the 3243 position of leucine tRNA. Internal Med (Tokyo, Japan). 2002;41(2):113–8.Google Scholar
  218. 218.
    Lowik MM, Hol FA, Steenbergen EJ, Wetzels JF, van den Heuvel LP. Mitochondrial tRNALeu(UUR) mutation in a patient with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis. Nephrol Dial Transplant. 2005;20(2):336–41.PubMedGoogle Scholar
  219. 219.
    Cheong HI, Chae JH, Kim JS, Park HW, Ha IS, Hwang YS, et al. Hereditary glomerulopathy associated with a mitochondrial tRNA(Leu) gene mutation. Pediatr Nephrol (Berlin, Germany). 1999;13(6):477–80.Google Scholar
  220. 220.
    Yamagata K, Muro K, Usui J, Hagiwara M, Kai H, Arakawa Y, et al. Mitochondrial DNA mutations in focal segmental glomerulosclerosis lesions. J Am Soc Nephrol. 2002;13(7):1816–23.PubMedGoogle Scholar
  221. 221.
    Guery B, Choukroun G, Noel LH, Clavel P, Rotig A, Lebon S, et al. The spectrum of systemic involvement in adults presenting with renal lesion and mitochondrial tRNA(Leu) gene mutation. J Am Soc Nephrol. 2003;14(8):2099–108.PubMedGoogle Scholar
  222. 222.
    Ueda Y, Ando A, Nagata T, Yanagida H, Yagi K, Sugimoto K, et al. A boy with mitochondrial disease: asymptomatic proteinuria without neuromyopathy. Pediatr Nephrol (Berlin, Germany). 2004;19(1):107–10.Google Scholar
  223. 223.
    Unal S, Kalkanoglu HS, Kocaefe C, Gucer S, Ozen S, Turanli G, et al. Four-month-old infant with focal segmental glomerulosclerosis and mitochondrial DNA deletion. J Child Neurol. 2005;20(1):83–4.PubMedGoogle Scholar
  224. 224.
    Emma F, Bertini E, Salviati L, Montini G. Renal involvement in mitochondrial cytopathies. Pediatr Nephrol. 2012;27(4):539–50.PubMedCentralPubMedGoogle Scholar
  225. 225.
    Hallman TM, Peng M, Meade R, Hancock WW, Madaio MP, Gasser DL. The mitochondrial and kidney disease phenotypes of kd/kd mice under germfree conditions. J Autoimmun. 2006;26(1):1–6.PubMedCentralPubMedGoogle Scholar
  226. 226.
    Saiki R, Lunceford AL, Shi Y, Marbois B, King R, Pachuski J, et al. Coenzyme Q10 supplementation rescues renal disease in Pdss2kd/kd mice with mutations in prenyl diphosphate synthase subunit 2. Am J Physiol Renal Physiol. 2008;295(5):F1535–44.PubMedCentralPubMedGoogle Scholar
  227. 227.
    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(2):345–9.PubMedCentralPubMedGoogle Scholar
  228. 228.
    Diomedi-Camassei F, Di Giandomenico S, Santorelli FM, Caridi G, Piemonte F, Montini G, et al. COQ2 nephropathy: a newly described inherited mitochondriopathy with primary renal involvement. J Am Soc Nephrol. 2007;18(10):2773–80.PubMedGoogle Scholar
  229. 229.
    Jakobs BS, van den Heuvel LP, Smeets RJ, de Vries MC, Hien S, Schaible T, et al. A novel mutation in COQ2 leading to fatal infantile multisystem disease. J Neurol Sci. 2013;326(1–2):24–8.PubMedGoogle Scholar
  230. 230.
    Mollet J, Giurgea I, Schlemmer D, Dallner G, Chretien D, Delahodde A, et al. Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidative phosphorylation disorders. J Clin Invest. 2007;117(3):765–72.PubMedCentralPubMedGoogle Scholar
  231. 231.
    Scalais E, Chafai R, Van Coster R, Bindl L, Nuttin C, Panagiotaraki C, et al. Early myoclonic epilepsy, hypertrophic cardiomyopathy and subsequently a nephrotic syndrome in a patient with CoQ10 deficiency caused by mutations in para-hydroxybenzoate-polyprenyl transferase (COQ2). Eur J Paediatr Neurol. 2013;17(6):625–30.PubMedGoogle Scholar
  232. 232.
    Montini G, Malaventura C, Salviati L. Early coenzyme Q10 supplementation in primary coenzyme Q10 deficiency. N Engl J Med. 2008;358(26):2849–50.PubMedGoogle Scholar
  233. 233.
    Lopez LC, Schuelke M, Quinzii CM, Kanki T, Rodenburg RJ, 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(6):1125–9.PubMedCentralPubMedGoogle Scholar
  234. 234.
    Hancock WW, Tsai TL, Madaio MP, Gasser DL. Cutting Edge: multiple autoimmune pathways in kd/kd mice. J Immunol. 2003;171(6):2778–81.PubMedGoogle Scholar
  235. 235.
    Barisoni L, Madaio MP, Eraso M, Gasser DL, Nelson PJ. The kd/kd mouse is a model of collapsing glomerulopathy. J Am Soc Nephrol. 2005;16(10):2847–51.PubMedCentralPubMedGoogle Scholar
  236. 236.
    Peng M, Jarett L, Meade R, Madaio MP, Hancock WW, George Jr AL, et al. Mutant prenyltransferase-like mitochondrial protein (PLMP) and mitochondrial abnormalities in kd/kd mice. Kidney Int. 2004;66(1):20–8.PubMedCentralPubMedGoogle Scholar
  237. 237.
    Heeringa SF, Chernin G, Chaki M, Zhou W, Sloan AJ, Ji Z, et al. COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness. J Clin Invest. 2011;121(5):2013–24.PubMedCentralPubMedGoogle Scholar
  238. 238.
    Ashraf S, Gee HY, Woerner S, Xie LX, Vega-Warner V, Lovric S, et al. ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption. J Clin Invest. 2013;123(12):5179–89.PubMedCentralPubMedGoogle Scholar
  239. 239.
    Turunen M, Olsson J, Dallner G. Metabolism and function of coenzyme Q. Biochim Biophys Acta. 2004;1660(1–2):171–99.PubMedGoogle Scholar
  240. 240.
    Badhwar A, Berkovic SF, Dowling JP, Gonzales M, Narayanan S, Brodtmann A, et al. Action myoclonus-renal failure syndrome: characterization of a unique cerebro-renal disorder. Brain. 2004;127(Pt 10):2173–82.PubMedGoogle Scholar
  241. 241.
    Balreira A, Gaspar P, Caiola D, Chaves J, Beirao I, Lima JL, et al. A nonsense mutation in the LIMP-2 gene associated with progressive myoclonic epilepsy and nephrotic syndrome. Hum Mol Genet. 2008;17(14):2238–43.PubMedGoogle Scholar
  242. 242.
    Berkovic SF, Dibbens LM, Oshlack A, Silver JD, Katerelos M, Vears DF, 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(3):673–84.PubMedCentralPubMedGoogle Scholar
  243. 243.
    Reczek D, Schwake M, Schroder J, Hughes H, Blanz J, Jin X, et al. LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase. Cell. 2007;131(4):770–83.PubMedGoogle Scholar
  244. 244.
    Eskelinen EL, Tanaka Y, Saftig P. At the acidic edge: emerging functions for lysosomal membrane proteins. Trends Cell Biol. 2003;13(3):137–45.PubMedGoogle Scholar
  245. 245.
    Gamp AC, Tanaka Y, Lullmann-Rauch R, Wittke D, D’Hooge R, De Deyn PP, et al. LIMP-2/LGP85 deficiency causes ureteric pelvic junction obstruction, deafness and peripheral neuropathy in mice. Hum Mol Genet. 2003;12(6):631–46.PubMedGoogle Scholar
  246. 246.
    Knipper M, Claussen C, Ruttiger L, Zimmermann U, Lullmann-Rauch R, Eskelinen EL, et al. Deafness in LIMP2-deficient mice due to early loss of the potassium channel KCNQ1/KCNE1 in marginal cells of the stria vascularis. J Physiol. 2006;576(Pt 1):73–86.PubMedCentralPubMedGoogle Scholar
  247. 247.
    Galloway WH, Mowat AP. Congenital microcephaly with hiatus hernia and nephrotic syndrome in two sibs. J Med Genet. 1968;5(4):319–21.PubMedCentralPubMedGoogle Scholar
  248. 248.
    Ekstrand JJ, Friedman AL, Stafstrom CE. Galloway-Mowat syndrome: neurologic features in two sibling pairs. Pediatr Neurol. 2012;47(2):129–32.PubMedGoogle Scholar
  249. 249.
    Shapiro LR, Duncan PA, Farnsworth PB, Lefkowitz M. Congenital microcephaly, hiatus hernia and nephrotic syndrome: an autosomal recessive syndrome. Birth Defects Orig Artic Ser. 1976;12(5):275–8.PubMedGoogle Scholar
  250. 250.
    Roos RA, Maaswinkel-Mooy PD, vd Loo EM, Kanhai HH. Congenital microcephaly, infantile spasms, psychomotor retardation, and nephrotic syndrome in two sibs. Eur J Pediatr. 1987;146(5):532–6.PubMedGoogle Scholar
  251. 251.
    Garty BZ, Eisenstein B, Sandbank J, Kaffe S, Dagan R, Gadoth N. Microcephaly and congenital nephrotic syndrome owing to diffuse mesangial sclerosis: an autosomal recessive syndrome. J Med Genet. 1994;31(2):121–5.PubMedCentralPubMedGoogle Scholar
  252. 252.
    Yalcinkaya F, Tumer N, Ekim M, Kuyucu S, Cakar N, Ensari C. Congenital microcephaly and infantile nephrotic syndrome–a case report. Pediatr Nephrol. 1994;8(1):72–3.PubMedGoogle Scholar
  253. 253.
    Yu CH, Tsai WS, Wang PJ, Tsau YK, Tseng GC, Wang TR. Congenital nephrotic syndrome with microcephaly: report of a case. J Formos Med Assoc. 1994;93(6):528–30.PubMedGoogle Scholar
  254. 254.
    Hashimoto K, Takeuchi Y, Kida Y, Hasegawa H, Kantake M, Sasaki A, et al. Three siblings of fatal infantile encephalopathy with olivopontocerebellar hypoplasia and microcephaly. Brain Dev. 1998;20(3):169–74.PubMedGoogle Scholar
  255. 255.
    de Vries BB, van’t Hoff WG, Surtees RA, Winter RM. Diagnostic dilemmas in four infants with nephrotic syndrome, microcephaly and severe developmental delay. Clin Dysmorphol. 2001;10(2):115–21.PubMedGoogle Scholar
  256. 256.
    Steiss JO, Gross S, Neubauer BA, Hahn A. Late-onset nephrotic syndrome and severe cerebellar atrophy in Galloway-Mowat syndrome. Neuropediatrics. 2005;36(5):332–5.PubMedGoogle Scholar
  257. 257.
    Cohen AH, Turner MC. Kidney in Galloway-Mowat syndrome: clinical spectrum with description of pathology. Kidney Int. 1994;45(5):1407–15.PubMedGoogle Scholar
  258. 258.
    Mildenberger E, Lennert T, Kunze J, Jandeck C, Waldherr R, Versmold H. Diffuse mesangial sclerosis: association with unreported congenital anomalies and placental enlargement. Acta Paediatr. 1998;87(12):1301–3.PubMedGoogle Scholar
  259. 259.
    Nakazato H, Hattori S, Karashima S, Kawano T, Seguchi S, Kanahori M, et al. Another autosomal recessive form of focal glomerulosclerosis with neurological findings. Pediatr Nephrol. 2002;17(1):16–9.PubMedGoogle Scholar
  260. 260.
    Shiihara T, Kato M, Kimura T, Matsunaga A, Joh K, Hayasaka K. Microcephaly, cerebellar atrophy, and focal segmental glomerulosclerosis in two brothers: a possible mild form of Galloway-Mowat syndrome. J Child Neurol. 2003;18(2):147–9.PubMedGoogle Scholar
  261. 261.
    Colin E, Huynh Cong E, Mollet G, Guichet A, Gribouval O, Arrondel C, et al. Loss-of-function mutations in WDR73 are responsible for Microcephaly and steroid-resistant nephrotic syndrome: Galloway-Mowat syndrome. Am J Hum Genet. 2014;95(6):637–48.PubMedCentralPubMedGoogle Scholar
  262. 262.
    Gee HY, Saisawat P, Ashraf S, Hurd TW, Vega-Warner V, Fang H, et al. ARHGDIA mutations cause nephrotic syndrome via defective RHO GTPase signaling. J Clin Invest. 2013;123(8):3243–53.PubMedCentralPubMedGoogle Scholar
  263. 263.
    Gupta IR, Baldwin C, Auguste D, Ha KC, El Andalousi J, Fahiminiya S, et al. ARHGDIA: a novel gene implicated in nephrotic syndrome. J Med Genet. 2013;50(5):330–8.PubMedCentralPubMedGoogle Scholar
  264. 264.
    Togawa A, Miyoshi J, Ishizaki H, Tanaka M, Takakura A, Nishioka H, et al. Progressive impairment of kidneys and reproductive organs in mice lacking Rho GDIalpha. Oncogene. 1999;18(39):5373–80.PubMedGoogle Scholar
  265. 265.
    Faul C, Asanuma K, Yanagida-Asanuma E, Kim K, Mundel P. Actin up: regulation of podocyte structure and function by components of the actin cytoskeleton. Trends Cell Biol. 2007;17(9):428–37.PubMedGoogle Scholar
  266. 266.
    Zhu L, Jiang R, Aoudjit L, Jones N, Takano T. Activation of RhoA in podocytes induces focal segmental glomerulosclerosis. J Am Soc Nephrol. 2011;22(9):1621–30.PubMedCentralPubMedGoogle Scholar
  267. 267.
    Scott RP, Hawley SP, Ruston J, Du J, Brakebusch C, Jones N, et al. Podocyte-specific loss of Cdc42 leads to congenital nephropathy. J Am Soc Nephrol. 2012;23(7):1149–54.PubMedCentralPubMedGoogle Scholar
  268. 268.
    Wang L, Ellis MJ, Gomez JA, Eisner W, Fennell W, Howell DN, et al. Mechanisms of the proteinuria induced by Rho GTPases. Kidney Int. 2012;81(11):1075–85.PubMedCentralPubMedGoogle Scholar
  269. 269.
    Shibata S, Nagase M, Yoshida S, Kawarazaki W, Kurihara H, Tanaka H, et al. Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease. Nat Med. 2008;14(12):1370–6.PubMedGoogle Scholar
  270. 270.
    Lemieux G, Neemeh JA. Charcot-Marie-Tooth disease and nephritis. Can Med Assoc J. 1967;97(20):1193–8.PubMedCentralPubMedGoogle Scholar
  271. 271.
    Toyota K, Ogino D, Hayashi M, Taki M, Saito K, Abe A, et al. INF2 mutations in Charcot-Marie-Tooth disease complicated with focal segmental glomerulosclerosis. J Peripher Nerv Syst. 2013;18(1):97–8.PubMedGoogle Scholar
  272. 272.
    Caridi G, Lugani F, Dagnino M, Gigante M, Iolascon A, Falco M, et al. Novel INF2 mutations in an Italian cohort of patients with focal segmental glomerulosclerosis, renal failure and Charcot-Marie-Tooth neuropathy. Nephrol Dial Transplant. 2014;29 Suppl 4:iv80–6.PubMedGoogle Scholar
  273. 273.
    Rodriguez PQ, Lohkamp B, Celsi G, Mache CJ, Auer-Grumbach M, Wernerson A, et al. Novel INF2 mutation p. L77P in a family with glomerulopathy and Charcot-Marie-Tooth neuropathy. Pediatr Nephrol. 2013;28(2):339–43.PubMedGoogle Scholar
  274. 274.
    Mademan I, Deconinck T, Dinopoulos A, Voit T, Schara U, Devriendt K, et al. De novo INF2 mutations expand the genetic spectrum of hereditary neuropathy with glomerulopathy. Neurology. 2013;81(22):1953–8.PubMedGoogle Scholar
  275. 275.
    Fine JD, Johnson LB, Weiner M, Stein A, Cash S, DeLeoz J, et al. Inherited epidermolysis bullosa and the risk of death from renal disease: experience of the National Epidermolysis Bullosa Registry. Am J Kidney Dis. 2004;44(4):651–60.PubMedGoogle Scholar
  276. 276.
    Sams Jr WM, Smith Jr JG. Epidermolysis bullosa acquisita, dermal elastosis amyloidosis. Arch Dermatol. 1964;90:137–42.PubMedGoogle Scholar
  277. 277.
    Kaneko K, Kakuta M, Ohtomo Y, Shimizu T, Yamashiro Y, Ogawa H, et al. Renal amyloidosis in recessive dystrophic epidermolysis bullosa. Dermatology. 2000;200(3):209–12.PubMedGoogle Scholar
  278. 278.
    Kambham N, Tanji N, Seigle RL, Markowitz GS, Pulkkinen L, Uitto J, et al. Congenital focal segmental glomerulosclerosis associated with beta4 integrin mutation and epidermolysis bullosa. Am J Kidney Dis. 2000;36(1):190–6.PubMedGoogle Scholar
  279. 279.
    Hata D, Miyazaki M, Seto S, Kadota E, Muso E, Takasu K, et al. Nephrotic syndrome and aberrant expression of laminin isoforms in glomerular basement membranes for an infant with Herlitz junctional epidermolysis bullosa. Pediatrics. 2005;116(4):e601–7.PubMedGoogle Scholar
  280. 280.
    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(16):1508–14.PubMedCentralPubMedGoogle Scholar
  281. 281.
    Nicolaou N, Margadant C, Kevelam SH, Lilien MR, Oosterveld MJ, Kreft M, et al. Gain of glycosylation in integrin alpha3 causes lung disease and nephrotic syndrome. J Clin Invest. 2012;122(12):4375–87.PubMedCentralPubMedGoogle Scholar
  282. 282.
    Kreidberg JA, Donovan MJ, Goldstein SL, Rennke H, Shepherd K, Jones RC, et al. Alpha 3 beta 1 integrin has a crucial role in kidney and lung organogenesis. Development. 1996;122(11):3537–47.PubMedGoogle Scholar
  283. 283.
    Karamatic Crew V, Burton N, Kagan A, Green CA, Levene C, Flinter F, et al. CD151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin. Blood. 2004;104(8):2217–23.PubMedGoogle Scholar
  284. 284.
    Sterk LM, Geuijen CA, van den Berg JG, Claessen N, Weening JJ, Sonnenberg A. Association of the tetraspanin CD151 with the laminin-binding integrins alpha3beta1, alpha6beta1, alpha6beta4 and alpha7beta1 in cells in culture and in vivo. J Cell Sci. 2002;115(Pt 6):1161–73.PubMedGoogle Scholar
  285. 285.
    Yauch RL, Berditchevski F, Harler MB, Reichner J, Hemler ME. Highly stoichiometric, stable, and specific association of integrin alpha3beta1 with CD151 provides a major link to phosphatidylinositol 4-kinase, and may regulate cell migration. Mol Biol Cell. 1998;9(10):2751–65.PubMedCentralPubMedGoogle Scholar
  286. 286.
    Yauch RL, Kazarov AR, Desai B, Lee RT, Hemler ME. Direct extracellular contact between integrin alpha(3)beta(1) and TM4SF protein CD151. J Biol Chem. 2000;275(13):9230–8.PubMedGoogle Scholar
  287. 287.
    Nishiuchi R, Takagi J, Hayashi M, Ido H, Yagi Y, Sanzen N, et al. Ligand-binding specificities of laminin-binding integrins: a comprehensive survey of laminin-integrin interactions using recombinant alpha3beta1, alpha6beta1, alpha7beta1 and alpha6beta4 integrins. Matrix Biol. 2006;25(3):189–97.PubMedGoogle Scholar
  288. 288.
    Baleato RM, Guthrie PL, Gubler MC, Ashman LK, Roselli S. Deletion of CD151 results in a strain-dependent glomerular disease due to severe alterations of the glomerular basement membrane. Am J Pathol. 2008;173(4):927–37.PubMedCentralPubMedGoogle Scholar
  289. 289.
    Sachs N, Kreft M, van den Bergh Weerman MA, Beynon AJ, Peters TA, Weening JJ, et al. Kidney failure in mice lacking the tetraspanin CD151. J Cell Biol. 2006;175(1):33–9.PubMedCentralPubMedGoogle Scholar
  290. 290.
    Motoyama O, Sugawara H, Hatano M, Fujisawa T, Iitaka K. Steroid-sensitive nephrotic syndrome in two families. Clin Exp Nephrol. 2009;13(2):170–3.PubMedGoogle Scholar
  291. 291.
    White RH. The familial nephrotic syndrome I A European survey. Clin Nephrol. 1973;1(4):215–9.PubMedGoogle Scholar
  292. 292.
    Bensman A, Vasmant D, Mougenot B, Baudon JJ, Muller JY. [Steroid-responsive nephrotic syndrome in infants: 2 familial case reports]. Arch Fr Pediatr. 1982;39(6):381–3.PubMedGoogle Scholar
  293. 293.
    Mallmann R. Idiopathic nephrotic syndrome and hexadactyly in two brothers. Pediatr Nephrol. 1998;12(5):417–9.PubMedGoogle Scholar
  294. 294.
    Fuchshuber A, Gribouval O, Ronner V, Kroiss S, Karle S, Brandis M, et al. Clinical and genetic evaluation of familial steroid-responsive nephrotic syndrome in childhood. J Am Soc Nephrol. 2001;12(2):374–8.PubMedGoogle Scholar
  295. 295.
    Kari JA, Sinnott P, Khan H, Trompeter RS, Snodgrass GJ. Familial steroid-responsive nephrotic syndrome and HLA antigens in Bengali children. Pediatr Nephrol. 2001;16(4):346–9.PubMedGoogle Scholar
  296. 296.
    Ruf RG, Fuchshuber A, Karle SM, Lemainque A, Huck K, Wienker T, et al. Identification of the first gene locus (SSNS1) for steroid-sensitive nephrotic syndrome on chromosome 2p. J Am Soc Nephrol. 2003;14(7):1897–900.PubMedGoogle Scholar
  297. 297.
    Landau D, Oved T, Geiger D, Abizov L, Shalev H, Parvari R. Familial steroid-sensitive nephrotic syndrome in Southern Israel: clinical and genetic observations. Pediatr Nephrol. 2007;22(5):661–9.PubMedGoogle Scholar
  298. 298.
    Chehade H, Cachat F, Girardin E, Rotman S, Correia AJ, Fellmann F, et al. Two new families with hereditary minimal change disease. BMC Nephrol. 2013;14:65.PubMedCentralPubMedGoogle Scholar
  299. 299.
    Gbadegesin RA, Adeyemo A, Webb NJ, Greenbaum LA, Abeyagunawardena A, Thalgahagoda S, et al. HLA-DQA1 and PLCG2 are candidate risk loci for childhood-onset steroid-sensitive nephrotic syndrome. J Am Soc Nephrol. 2014 [epub ahead of print].Google Scholar
  300. 300.
    Gee HY, 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(6):884–90.PubMedCentralPubMedGoogle Scholar
  301. 301.
    Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010;329(5993):841–5.PubMedCentralPubMedGoogle Scholar
  302. 302.
    Giglio S, Provenzano A, Mazzinghi B, Becherucci F, Giunti L, Sansavini G, et al. Heterogeneous genetic alterations in sporadic nephrotic syndrome associate with resistance to immunosuppression. J Am Soc Nephrol. 2014;26(1):230–6.PubMedGoogle Scholar
  303. 303.
    McCarthy HJ, Bierzynska A, Wherlock M, Ognjanovic M, Kerecuk L, Hegde S, et al. Simultaneous sequencing of 24 genes associated with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2013;8(4):637–48.PubMedCentralPubMedGoogle Scholar
  304. 304.
    Korkmaz E, Lipska-Ziętkiewicz BS, Boyer O, Gribouval O, Fourrage C, Tabatabaei M, Schnaidt S, Gucer S, Kaymaz F, Arici M, Dinckan A, Mir S, Bayazit AK, Emre S, Balat A, Rees L, Shroff R, Bergmann C, Mourani C, Antignac C, Ozaltin F, Schaefer F, PodoNet Consortium. ADCK4-associated glomerulopathy causes adolescence-onset FSGS. J Am Soc Nephrol. pii: ASN.2014121240. 2015 [epub ahead of print].Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Olivia Boyer
    • 1
    • 2
    • 3
  • Kálmán Tory
    • 2
    • 4
  • Eduardo Machuca
    • 5
  • Corinne Antignac
    • 2
    • 3
    • 6
  1. 1.Pediatric NephrologyMARHEA reference center, Necker - Enfants Malades HospitalParisFrance
  2. 2.Laboratory of Hereditary Kidney DiseasesInserm UMR 1163ParisFrance
  3. 3.Paris DescartesSorbonne Paris Cité University, Imagine InstituteParisFrance
  4. 4.Department of PediatricsSemmelweis UniversityBudapestHungary
  5. 5.Department of NephrologyMedical School, Pontificia Universidad Católica de ChileSantiagoChile
  6. 6.Department of GeneticsMARHEA reference center, Necker – Enfants Malades HospitalParisFrance

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