Nephronophthisis–Medullary Cystic Kidney Disease in Children

  • Friedhelm Hildebrandt
Living reference work entry

Latest version View entry history


Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that constitutes one of the most frequent genetic causes for end-stage kidney disease (ESKD) in the first three decades of life (Hildebrandt and Otto, Nat Rev Genet 2005; Smith and Graham, Am J Dis Child 69:369–377, 1945; Fanconi et al., Helv Pediatr Acta 6:1–49, 1951; Hildebrandt and Zhou, J Am Soc Nephrol 18(6):1855–1871, 2007). Three clinical forms of NPHP have been distinguished by age of onset of ESKD: infantile (Gagnadoux et al., Pediatr Nephrol 3(1):50–55, 1989; Otto et al. 2003), juvenile (Hildebrandt et al., Clin Investig 70(9):802–808, 1992), and adolescent NPHP (Omran et al., Am J Hum Genet 66(1):118–127, 2000), which manifest with ESKD at median ages of 1 year, 13 years, and 15 years, respectively. Initial symptoms are relatively mild with the exception of infantile NPHP type 2. They consist of polyuria, polydipsia with regular fluid intake at nighttime, secondary enuresis, and anemia (Omran et al., Am J Hum Genet 66(1):118–127, 2000). A slightly raised serum creatinine is noted at an average age of 9 years, before ESKD invariably develops within a few years. Renal ultrasound reveals increased echogenicity. Beyond the age of 9 years, cysts appear at the corticomedullary junction within kidneys of normal or slightly reduced size (Blowey et al., Pediatr Nephrol 10(1):22–24, 1996). Renal histology reveals a characteristic triad of tubular basement membrane disruption, tubulointerstitial nephropathy, and cysts (Waldherr et al., Virchows Arch A Pathol Anat Histol 394(3):235–254, 1982; Zollinger et al., Helv Paediatr Acta 35(6):509–530, 1980). In nephronophthisis cysts arise from the corticomedullary junction of the kidneys. Because kidney size is normal or slightly reduced, cysts seem to develop e vacuo through loss of normal tissue. This is in contrast to polycystic kidney disease, where cysts are distributed evenly and lead to gross enlargement of the kidneys (Hildebrandt F (1999) Juvenile nephronophthisis. In: Harmon WE (ed) Pediatric nephrology. Williams & Wilkins, Baltimore). NPHP is part of a broad spectrum of renal cystic/degenerative diseases that often include extrarenal manifestations. Over 80 recessive single-gene causes have been identified. Because the related gene products localize to primary cilia and centrosomes, the term “NPHP-related ciliopathies (NPHP-RC)” is now used for these disorders.


Retinitis Pigmentosa Primary Cilium Retinal Degeneration Situs Inversus Planar Cell Polarity 
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.


  1. 1.
    Ala-Mello S, Kivivuori SM, Ronnholm KA, et al. Mechanism underlying early anaemia in children with familial juvenile nephronophthisis. Pediatr Nephrol. 1996;10(5):578–81.PubMedGoogle Scholar
  2. 2.
    Amirou M, Bourdat-Michel G, Pinel N, et al. Successful renal transplantation in Jeune syndrome type 2. Pediatr Nephrol. 1998;12(4):293–4.PubMedGoogle Scholar
  3. 3.
    Andersen JS, Wilkinson CJ, Mayor T, et al. Proteomic characterization of the human centrosome by protein correlation profiling. Nature. 2003;426(6966):570–4.PubMedGoogle Scholar
  4. 4.
    Antignac C, Arduy CH, Beckmann JS, et al. A gene for familial juvenile nephronophthisis (recessive medullary cystic kidney disease) maps to chromosome 2p. Nat Genet. 1993;3(4):342–5.PubMedGoogle Scholar
  5. 5.
    Attanasio M, Uhlenhaut NH, Sousa VH, et al. Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis. Nat Genet. 2007;39(8):1018–24.PubMedGoogle Scholar
  6. 6.
    Baala L, Audollent S, Martinovic J, et al. Pleiotropic effects of CEP290 (NPHP6) mutations extend to Meckel syndrome. Am J Hum Genet. 2007;81(1):170–9.PubMedCentralPubMedGoogle Scholar
  7. 7.
    Badano JL, Kim JC, Hoskins BE, et al. Heterozygous mutations in BBS1, BBS2 and BBS6 have a potential epistatic effect on Bardet-Biedl patients with two mutations at a second BBS locus. Hum Mol Genet. 2003;12(14):1651–9.PubMedGoogle Scholar
  8. 8.
    Badano JL, Teslovich TM, Katsanis N. The centrosome in human genetic disease. Nat Rev Genet. 2005;6(3):194–205.PubMedGoogle Scholar
  9. 9.
    Bae YK, Qin H, Knobel KM, et al. General and cell-type specific mechanisms target TRPP2/PKD-2 to cilia. Development. 2006;133(19):3859–70.PubMedGoogle Scholar
  10. 10.
    Bae YK, Lyman-Gingerich J, Barr MM, Knobel KM. Identification of genes involved in the ciliary trafficking of C. elegans PKD-2. Dev Dyn. 2008;273(8):2021–9.Google Scholar
  11. 11.
    Barr MM, DeModena J, Braun D, et al. The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway. Curr Biol. 2001;11(17):1341–6.PubMedGoogle Scholar
  12. 12.
    Beales PL, Badano JL, Ross AJ, et al. Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non-Mendelian Bardet-Biedl syndrome. Am J Hum Genet. 2003;72(5):1187–99.PubMedCentralPubMedGoogle Scholar
  13. 13.
    Beales PL, Bland E, Tobin JL, et al. IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy. Nat Genet. 2007;39(6):727–9.PubMedGoogle Scholar
  14. 14.
    Benzing T, Walz G. Cilium-generated signaling: a cellular GPS? Curr Opin Nephrol Hypertens. 2006;15(3):245–9.PubMedGoogle Scholar
  15. 15.
    Benzing T, Gerke P, Hopker K, et al. Nephrocystin interacts with Pyk2, p130(Cas), and tensin and triggers phosphorylation of Pyk2. Proc Natl Acad Sci U S A. 2001;98(17):9784–9.PubMedCentralPubMedGoogle Scholar
  16. 16.
    Bergmann C, Fliegauf M, Bruchle NO, et al. Loss of nephrocystin-3 function can cause embryonic lethality, Meckel-Gruber-like syndrome, situs inversus, and renal-hepatic-pancreatic dysplasia. Am J Hum Genet. 2008;82(4):959–70.PubMedCentralPubMedGoogle Scholar
  17. 17.
    Betts PR, Forest-Hay I. Juvenile nephronophthisis. Lancet. 1973;2:475–8.PubMedGoogle Scholar
  18. 18.
    Betz R, Rensing C, Otto E, et al. Children with ocular motor apraxia type Cogan carry deletions in the gene (NPHP1) for juvenile nephronophthisis. J Pediatr. 2000;136(6):828–31.PubMedGoogle Scholar
  19. 19.
    Bisgrove BW, Yost HJ. The roles of cilia in developmental disorders and disease. Development. 2006;133(21):4131–43.PubMedGoogle Scholar
  20. 20.
    Bleyer AJ, Hart TC. Medullary cystic kidney disease type 2. Am J Kidney Dis. 2004;43(6):1142; author reply 1142–3.PubMedGoogle Scholar
  21. 21.
    Blowey DL, Querfeld U, Geary D, et al. Ultrasound findings in juvenile nephronophthisis. Pediatr Nephrol. 1996;10(1):22–4.PubMedGoogle Scholar
  22. 22.
    Bodaghi E, Honarmand MT, Ahmadi M. Infantile nephronophthisis. Int J Pediatr Nephrol. 1987;8(4):207–10.PubMedGoogle Scholar
  23. 23.
    Boichis H, Passwell J, David R, Miller H. Congenital hepatic fibrosis and nephronophthisis. A family study. Q J Med. 1973;42(165):221–33.PubMedGoogle Scholar
  24. 24.
    Bukanov NO, Smith LA, Klinger KW, et al. Long-lasting arrest of murine polycystic kidney disease with CDK inhibitor roscovitine. Nature. 2006;444(7121):949–52.PubMedGoogle Scholar
  25. 25.
    Burke JR, Inglis JA, Craswell PW, et al. Juvenile nephronophthisis and medullary cystic disease – the same disease (report of a large family with medullary cystic disease associated with gout and epilepsy). Clin Nephrol. 1982;18(1):1–8.PubMedGoogle Scholar
  26. 26.
    Cacchi R, Ricci V. Sopra una rara e forse ancora non descritta effezione cistica della piramidi renali (“rene a spugna”). Atti Soc Ital Urol. 1948;5:59.Google Scholar
  27. 27.
    Cantani A, Bamonte G, Ceccoli D. Familial juvenile nephronophthisis. Clin Pediatr. 1986;25:90–5.Google Scholar
  28. 28.
    Caridi G, Murer L, Bellantuono R, et al. Renal-retinal syndromes: association of retinal anomalies and recessive nephronophthisis in patients with homozygous deletion of the NPH1 locus. Am J Kidney Dis. 1998;32(6):1059–62.PubMedGoogle Scholar
  29. 29.
    Castori M, Valente EM, Donati MA, et al. NPHP1 gene deletion is a rare cause of Joubert syndrome related disorders. J Med Genet. 2005;42(2), e9.PubMedCentralPubMedGoogle Scholar
  30. 30.
    Chaki M, Airik R, Ghosh AK, Giles RH, Chen R, Slaats GG, Wang H, Hurd TW, Zhou W, Cluckey A, Gee HY, Ramaswami G, Hong CJ, Hamilton BA, Cervenka I, Ganji RS, Bryja V, Arts HH, van Reeuwijk J, Oud MM, Letteboer SJ, Roepman R, Husson H, Ibraghimov-Beskrovnaya O, Yasunaga T, Walz G, Eley L, Sayer JA, Schermer B, Liebau MC, Benzing T, Le Corre S, Drummond I, Janssen S, Allen SJ, Natarajan S, O’Toole JF, Attanasio M, Saunier S, Antignac C, Koenekoop RK, Ren H, Lopez I, Nayir A, Stoetzel C, Dollfus H, Massoudi R, Gleeson JG, Andreoli SP, Doherty DG, Lindstrad A, Golzio C, Katsanis N, Pape L, Abboud EB, Al-Rajhi AA, Lewis RA, Omran H, Lee EY, Wang S, Sekiguchi JM, Saunders R, Johnson CA, Garner E, Vanselow K, Andersen JS, Shlomai J, Nurnberg G, Nurnberg P, Levy S, Smogorzewska A, Otto EA, Hildebrandt F. Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling. Cell. 2012;150(3):533–48.PubMedCentralPubMedGoogle Scholar
  31. 31.
    Chamberlin BC, Hagge WW, Stickler GB. Juvenile nephronophthisis and medullary cystic disease. Mayo Clin Proc. 1977;52(8):485–91.PubMedGoogle Scholar
  32. 32.
    Chance PF, Cavalier L, Satran D, et al. Clinical nosologic and genetic aspects of Joubert and related syndromes. J Child Neurol. 1999;14(10):660–6; discussion 669–72.PubMedGoogle Scholar
  33. 33.
    Chang B, Khanna H, Hawes N, et al. In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse. Hum Mol Genet. 2006;15(11):1847–57.PubMedCentralPubMedGoogle Scholar
  34. 34.
    Choi HJ, Lin JR, Vannier JB, Slaats GG, Kile AC, Paulsen RD, Manning DK, Beier DR, Giles RH, Boulton SJ, Cimprich KA. NEK8 links the ATR-regulated replication stress response and S phase CDK activity to renal ciliopathies. Mol Cell. 2013;51(4):423-39. doi:10.1016/j.molcel.2013.08.006.PubMedCentralPubMedGoogle Scholar
  35. 35.
    Christodoulou K, Tsingis M, Stavrou C, et al. Chromosome 1 localization of a gene for autosomal dominant medullary cystic kidney disease. Hum Mol Genet. 1998;7(5):905–11.PubMedGoogle Scholar
  36. 36.
    Costet C, Betis F, Berard E, et al. Pigmentosum retinis and tubulo-interstitial nephronophtisis in Sensenbrenner syndrome: a case report. J Fr Ophtalmol. 2000;23(2):158–60.PubMedGoogle Scholar
  37. 37.
    Dahan K, Fuchshuber A, Adamis S, et al. Familial juvenile hyperuricemic nephropathy and autosomal dominant medullary cystic kidney disease type 2: two facets of the same disease? J Am Soc Nephrol. 2001;12(11):2348–57.PubMedGoogle Scholar
  38. 38.
    Dahan K, Devuyst O, Smaers M, et al. A cluster of mutations in the UMOD gene causes familial juvenile hyperuricemic nephropathy with abnormal expression of uromodulin. J Am Soc Nephrol. 2003;14(11):2883–93.PubMedGoogle Scholar
  39. 39.
    Delaney V, Mullaney J, Bourke E. Juvenile nephronophthisis, congenital hepatic fibrosis and retinal hypoplasia in twins. Q J Med. 1978;47(187):281–90.PubMedGoogle Scholar
  40. 40.
    Delous M, Baala L, Salomon R, et al. The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. Nat Genet. 2007;39(7):875–81.PubMedGoogle Scholar
  41. 41.
    den Hollander AI, Koenekoop RK, Yzer S, et al. Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis. Am J Hum Genet. 2006;79(3):556–61.Google Scholar
  42. 42.
    Di Rocco M, Picco P, Arslanian A, et al. Retinitis pigmentosa, hypopituitarism, nephronophthisis, and mild skeletal dysplasia (RHYNS): a new syndrome? Am J Med Genet. 1997;73(1):1–4.PubMedGoogle Scholar
  43. 43.
    Donaldson MD, Warner AA, Trompeter RS, et al. Familial juvenile nephronophthisis, Jeune’s syndrome, and associated disorders. Arch Dis Child. 1985;60(5):426–34.PubMedCentralPubMedGoogle Scholar
  44. 44.
    Donaldson JC, Dempsey PJ, Reddy S, et al. Crk-associated substrate p130(Cas) interacts with nephrocystin and both proteins localize to cell-cell contacts of polarized epithelial cells. Exp Cell Res. 2000;256(1):168–78.PubMedGoogle Scholar
  45. 45.
    Donaldson JC, Dise RS, Ritchie MD, Hanks SK. Nephrocystin-conserved domains involved in targeting to epithelial cell-cell junctions, interaction with filamins, and establishing cell polarity. J Biol Chem. 2002;277(32):29028–35.PubMedGoogle Scholar
  46. 46.
    Efimenko E, Bubb K, Mak HY, et al. Analysis of xbx genes in C. Elegans Dev. 2005;132(8):1923–34.Google Scholar
  47. 47.
    Fanconi G, Hanhart E, Albertini A. Die familiäre juvenile nephronophthise. Helv Pediatr Acta. 1951;6:1–49.Google Scholar
  48. 48.
    Fischer E, Legue E, Doyen A, et al. Defective planar cell polarity in polycystic kidney disease. Nat Genet. 2006;38(1):21–3.PubMedGoogle Scholar
  49. 49.
    Fliegauf M, Horvath J, von Schnakenburg C, et al. Nephrocystin specifically localizes to the transition zone of renal and respiratory cilia and photoreceptor connecting cilia. J Am Soc Nephrol. 2006;17(9):2424–33.PubMedGoogle Scholar
  50. 50.
    Fuchshuber A, Deltas CC, Berthold S, et al. Autosomal dominant medullary cystic kidney disease: evidence of gene locus heterogeneity. Nephrol Dial Transplant. 1998;13(8):1955–7.PubMedGoogle Scholar
  51. 51.
    Fuchshuber A, Kroiss S, Karle S, et al. Refinement of the gene locus for autosomal dominant medullary cystic kidney disease type 1 (MCKD1) and construction of a physical and partial transcriptional map of the region. Genomics. 2001;72(3):278–84.PubMedGoogle Scholar
  52. 52.
    Fyhrquist FY, Klockars M, Gordin A, et al. Hyperreninemia, lysozymuria, and erythrocytosis in Fanconi syndrome with medullary cystic kidney. Acta Med Scand. 1980;207(5):359–65.PubMedGoogle Scholar
  53. 53.
    Gardner KD. Evolution of clinical signs in adult-onset cystic disease of the renal medulla. Ann Intern Med. 1971;74:47–54.PubMedGoogle Scholar
  54. 54.
    Gardner Jr KD. Juvenile nephronophthisis and renal medullary cystic disease. Perspect Nephrol Hypertens. 1976;4:173–85.PubMedGoogle Scholar
  55. 55.
    Garel LA, Habib R, Pariente D, et al. Juvenile nephronophthisis: sonographic appearance in children with severe uremia. Radiology. 1984;151(1):93–5.PubMedGoogle Scholar
  56. 56.
    Gattone 2nd VH, Wang X, Harris PC, Torres VE. Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat Med. 2003;9(10):1323–6.PubMedGoogle Scholar
  57. 57.
    Gee HY, Saisawat P, Ashraf S, Hurd TW, Vega-Warner V, Fang H, Beck BB, Gribouval O, Zhou W, Diaz KA, Natarajan S, Wiggins RC, Lovric S, Chernin G, Schoeb DS, Ovunc B, Frishberg Y, Soliman NA, Fathy HM, Goebel H, Hoefele J, Weber LT, Innis JW, Faul C, Han Z, Washburn J, Antignac C, Levy S, Otto EA, Hildebrandt F. ARHGDIA mutations cause nephrotic syndrome via defective RHO GTPase signaling. J Clin Invest. 2013;123(8):3243-53. doi:10.1172/JCI69134. Epub 2013 Jul 8.PubMedCentralPubMedGoogle Scholar
  58. 58.
    Germino GG. Linking cilia to Wnts. Nat Genet. 2005;37(5):455–7.PubMedGoogle Scholar
  59. 59.
    Giselson N, Heinegard D, Holmberg CG, et al. Renal medullary cystic disease or familial juvenile nephronophthisis: a renal tubular disease. Biochemical findings in two siblings. Am J Med. 1970;48(2):174–84.PubMedGoogle Scholar
  60. 60.
    Gleeson JG, Keeler LC, Parisi MA, et al. Molar tooth sign of the midbrain-hindbrain junction: occurrence in multiple distinct syndromes. Am J Med Genet. 2004;125A(2):125–34; discussion 117.PubMedGoogle Scholar
  61. 61.
    Goldman SH, Walker SR, Merigan Jr TC, et al. Hereditary occurrence of cystic disease of the renal medulla. N Engl J Med. 1966;274(18):984–92.PubMedGoogle Scholar
  62. 62.
    Gretz N. Rate of deterioration of renal function in juvenile nephronophthisis. Pediatr Nephrol. 1989;3:56–60.PubMedGoogle Scholar
  63. 63.
    Haider NB, Carmi R, Shalev H, et al. A Bedouin kindred with infantile nephronophthisis demonstrates linkage to chromosome 9 by homozygosity mapping. Am J Hum Genet. 1998;63(5):1404–10.PubMedCentralPubMedGoogle Scholar
  64. 64.
    Halbritter J, Bizet AA, Schmidts M, Porath JD, Braun DA, Gee HY, McInerney-Leo AM, Krug P, Filhol E, Davis EE, Airik R, Czarnecki PG, Lehman AM, Trnka P, Nitschké P, Bole-Feysot C, Schueler M, Knebelmann B, Burtey S, Szabó AJ, Tory K, Leo PJ, Gardiner B, McKenzie FA, Zankl A, Brown MA, Hartley JL, Maher ER, Li C, Leroux MR, Scambler PJ, Zhan SH, Jones SJ, Kayserili H, Tuysuz B, Moorani KN, Constantinescu A, Krantz ID, Kaplan BS, Shah JV, UK10K Consortium, Hurd TW, Doherty D, Katsanis N, Duncan EL, Otto EA, Beales PL, Mitchison HM, Saunier S, Hildebrandt F. Defects in the IFT-B component IFT172 cause Jeune and Mainzer-Saldino syndromes in humans. Am J Hum Genet. 2013;93(5):915–25.PubMedCentralPubMedGoogle Scholar
  65. 65.
    Hart TC, Gorry MC, Hart PS, et al. Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy. J Med Genet. 2002;39(12):882–92.PubMedCentralPubMedGoogle Scholar
  66. 66.
    Hateboer N, Gumbs C, Teare MD, et al. Confirmation of a gene locus for medullary cystic kidney disease (MCKD2) on chromosome 16p12. Kidney Int. 2001;60(4):1233–9.PubMedGoogle Scholar
  67. 67.
    Hildebrandt F. Pediatric nephrology. Baltimore: Williams & Wilkins; 1999.Google Scholar
  68. 68.
    Hildebrandt F, Otto EA. Primary cilia: a unifying pathogenic concept for cystic kidney disease? Nat Rev Genet. 2005;6(12):928–40.Google Scholar
  69. 69.
    Hildebrandt F, Zhou W. Nephronophthisis-associated ciliopathies. J Am Soc Nephrol. 2007;18(6):1855–71.PubMedGoogle Scholar
  70. 70.
    Hildebrandt F, Waldherr R, Kutt R, Brandis M. The nephronophthisis complex: clinical and genetic aspects. Clin Investig. 1992;70(9):802–8.PubMedGoogle Scholar
  71. 71.
    Hildebrandt F, Singh-Sawhney I, Schnieders B, et al. Mapping of a gene for familial juvenile nephronophthisis: refining the map and defining flanking markers on chromosome 2. APN Study Group. Am J Hum Genet. 1993;53(6):1256–61.PubMedCentralPubMedGoogle Scholar
  72. 72.
    Hildebrandt F, Cybulla M, Strahm B, et al. Physical mapping of the gene for juvenile nephronophthisis (NPH1) by construction of a complete YAC contig of 7 Mb on chromosome 2q13. Cytogenet Cell Genet. 1996;73(3):235–9.PubMedGoogle Scholar
  73. 73.
    Hildebrandt F, Otto E, Rensing C, et al. A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1. Nat Genet. 1997;17(2):149–53.PubMedGoogle Scholar
  74. 74.
    Hildebrandt F, Strahm B, Nothwang HG, et al. Molecular genetic identification of families with juvenile nephronophthisis type 1: rate of progression to renal failure. APN Study Group. Arbeitsgemeinschaft fur Padiatrische Nephrologie. Kidney Int. 1997;51(1):261–9.PubMedGoogle Scholar
  75. 75.
    Hildebrandt F, Rensing C, Betz R, et al. Establishing an algorithm for molecular genetic diagnostics in 127 families with juvenile nephronophthisis. Kidney Int. 2001;59(2):434–45.PubMedGoogle Scholar
  76. 76.
    Hildebrandt F, Benzing T, Katsanis N. Ciliopathies. N Engl J Med. 2011;364(16):1533–43.PubMedCentralPubMedGoogle Scholar
  77. 77.
    Hoefele J, Wolf MT, O’Toole JF, et al. Evidence of oligogenic inheritance in nephronophthisis. J Am Soc Nephrol. 2007;18(10):2789–95.PubMedGoogle Scholar
  78. 78.
    Huangfu D, Liu A, Rakeman AS, et al. Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature. 2003;426(6962):83–7.PubMedGoogle Scholar
  79. 79.
    Igarashi P, Somlo S. Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol. 2002;13(9):2384–98.PubMedGoogle Scholar
  80. 80.
    Ivemark BI, Ljungqvist A, Barry A. Juvenile nephronophthisis. Part 2. A histologic and microangiographic study. Acta Paediatr. 1960;49:480–7.PubMedGoogle Scholar
  81. 81.
    Jauregui AR, Barr MM. Functional characterization of the C. elegans nephrocystins NPHP-1 and NPHP-4 and their role in cilia and male sensory behaviors. Exp Cell Res. 2005;305(2):333–42.PubMedGoogle Scholar
  82. 82.
    Jauregui AR, Nguyen KC, Hall DH, Barr MM. The Caenorhabditis elegans nephrocystins act as global modifiers of cilium structure. J Cell Biol. 2008;180(5):973–88.PubMedCentralPubMedGoogle Scholar
  83. 83.
    Jeune M, Beraud C, Carron R. Dystrophie thoracique asphyxiante de caractere familial. [Asphyxiating thoracic dystrophy with familial characteristics]. Arch Fr Pediatr. 1955;12(8):886–91.PubMedGoogle Scholar
  84. 84.
    Joubert M, Eisenring JJ, Robb JP, Andermann F. Familial agenesis of the cerebellar vermis. A syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation. Neurology. 1969;19(9):813–25.PubMedGoogle Scholar
  85. 85.
    Keeler LC, Marsh SE, Leeflang EP, et al. Linkage analysis in families with Joubert syndrome plus oculo-renal involvement identifies the CORS2 locus on chromosome 11p12-q13.3. Am J Hum Genet. 2003;73(3):656–62.PubMedCentralPubMedGoogle Scholar
  86. 86.
    Khaddour R, Smith U, Baala L, et al. Spectrum of MKS1 and MKS3 mutations in Meckel syndrome: a genotype-phenotype correlation. Mutation in brief #960. Online. Hum Mutat. 2007;28(5):523–4.PubMedGoogle Scholar
  87. 87.
    Kirby A, Gnirke A, Jaffe DB, Barešová V, Pochet N, Blumenstiel B, Ye C, Aird D, Stevens C, Robinson JT, Cabili MN, Gat-Viks I, Kelliher E, Daza R, DeFelice M, Hůlková H, Sovová J, Vylet’al P, Antignac C, Guttman M, Handsaker RE, Perrin D, Steelman S, Sigurdsson S, Scheinman SJ, Sougnez C, Cibulskis K, Parkin M, Green T, Rossin E, Zody MC, Xavier RJ, Pollak MR, Alper SL, Lindblad-Toh K, Gabriel S, Hart PS, Regev A, Nusbaum C, Kmoch S, Bleyer AJ, Lander ES, Daly MJ. Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing. Nat Genet. 2013;45(3):299–303. doi:10.1038/ng.2543. Epub 2013 Feb 10.PubMedCentralPubMedGoogle Scholar
  88. 88.
    Kiser RL, Wolf MT, Martin JL, et al. Medullary cystic kidney disease type 1 in a large Native-American kindred. Am J Kidney Dis. 2004;44(4):611–7.PubMedGoogle Scholar
  89. 89.
    Kleinknecht C. The inheritance of nephronophthisis, Inheritance of kidney and urinary tract diseases, vol. 9. Boston: Kluwer; 1989. p. 464.Google Scholar
  90. 90.
    Kozminski KG, Johnson KA, Forscher P, Rosenbaum JL. A motility in the eukaryotic flagellum unrelated to flagellar beating. Proc Natl Acad Sci U S A. 1993;90(12):5519–23.PubMedCentralPubMedGoogle Scholar
  91. 91.
    Kumada S, Hayashi M, Arima K, et al. Renal disease in Arima syndrome is nephronophthisis as in other Joubert-related Cerebello-oculo-renal syndromes. Am J Med Genet A. 2004;131(1):71–6.PubMedGoogle Scholar
  92. 92.
    Kyttala M, Tallila J, Salonen R, et al. MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome. Nat Genet. 2006;38(2):155–7.PubMedGoogle Scholar
  93. 93.
    Lans H, Marteijn JA, Schumacher B, Hoeijmakers JH, Jansen G, Vermeulen W. Involvement of global genome repair, transcription coupled repair, and chromatin remodeling in UV DNA damage response changes during development. PLoS Genet. 2010;6(5):e1000941. doi:10.1371/journal.pgen.1000941.PubMedCentralPubMedGoogle Scholar
  94. 94.
    Lin F, Hiesberger T, Cordes K, et al. Kidney-specific inactivation of the KIF3A subunit of kinesin-II inhibits renal ciliogenesis and produces polycystic kidney disease. Proc Natl Acad Sci U S A. 2003;100(9):5286–91.PubMedCentralPubMedGoogle Scholar
  95. 95.
    Liu S, Lu W, Obara T, et al. A defect in a novel Nek-family kinase causes cystic kidney disease in the mouse and in zebrafish. Development. 2002;129(24):5839–46.PubMedGoogle Scholar
  96. 96.
    Loken AC, Hanssen O, Halvorsen S, Jolster NJ. Hereditary renal dysplasia and blindness. Acta Paediatr. 1961;50:177–84.PubMedGoogle Scholar
  97. 97.
    Mainzer F, Saldino RM, Ozonoff MB, Minagi H. Familial nephropathy associated with retinitis pigmentosa, cerebellar ataxia and skeletal abnormalities. Am J Med. 1970;49(4):556–62.PubMedGoogle Scholar
  98. 98.
    McGrath J, Somlo S, Makova S, et al. Two populations of node monocilia initiate left-right asymmetry in the mouse. Cell. 2003;114(1):61–73.PubMedGoogle Scholar
  99. 99.
    McGregor AR, Bailey RR. Nephronophthisis-cystic renal medulla complex: diagnosis by computerized tomography. Nephron. 1989;53(1):70–2.PubMedGoogle Scholar
  100. 100.
    Mf G, Jl B, Broyer M, Habib R. Infantile chronic tubulo-interstitial nephritis with cortical microcysts: variant of nephronophthisis or new disease entity? Pediatr Nephrol. 1989;3(1):50–5.Google Scholar
  101. 101.
    Mochizuki T, Saijoh Y, Tsuchiya K, et al. Cloning of inv, a gene that controls left/right asymmetry and kidney development. Nature. 1998;395(6698):177–81.PubMedGoogle Scholar
  102. 102.
    Mollet G, Salomon R, Gribouval O, et al. The gene mutated in juvenile nephronophthisis type 4 encodes a novel protein that interacts with nephrocystin. Nat Genet. 2002;32(2):300–5.PubMedGoogle Scholar
  103. 103.
    Mollet G, Silbermann F, Delous M, et al. Characterization of the nephrocystin/nephrocystin-4 complex and subcellular localization of nephrocystin-4 to primary cilia and centrosomes. Hum Mol Genet. 2005;14(5):645–56.PubMedGoogle Scholar
  104. 104.
    Morgan D, Turnpenny L, Goodship J, et al. Inversin, a novel gene in the vertebrate left-right axis pathway, is partially deleted in the inv mouse. Nat Genet. 1998;20(2):149–56.PubMedGoogle Scholar
  105. 105.
    Moudgil A, Bagga A, Kamil ES, et al. Nephronophthisis associated with Ellis-van Creveld syndrome. Pediatr Nephrol. 1998;12(1):20–2.PubMedGoogle Scholar
  106. 106.
    Mykytyn K, Sheffield VC. Establishing a connection between cilia and Bardet-Biedl Syndrome. Trends Mol Med. 2004;10(3):106–9.PubMedGoogle Scholar
  107. 107.
    Nauli SM, Alenghat FJ, Luo Y, et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet. 2003;33(2):129–37.PubMedGoogle Scholar
  108. 108.
    Nothwang HG, Strahm B, Denich D, et al. Molecular cloning of the interleukin-1 gene cluster: construction of an integrated YAC/PAC contig and a partial transcriptional map in the region of chromosome 2q13. Genomics. 1997;41(3):370–8.PubMedGoogle Scholar
  109. 109.
    Nurnberger J, Bacallao RL, Phillips CL. Inversin forms a complex with catenins and N-cadherin in polarized epithelial cells. Mol Biol Cell. 2002;13(9):3096–106.PubMedCentralPubMedGoogle Scholar
  110. 110.
    O’Toole JF, Otto E, Frishberg Y, Hildebrandt F. Retinitis pigmentosa and renal failure in a patient with mutations in inversin. J Am Soc Nephrol. 2004;15:215A.Google Scholar
  111. 111.
    Olbrich H, Fliegauf M, Hoefele J, et al. Mutations in a novel gene, NPHP3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosis. Nat Genet. 2003;34(4):455–9.PubMedGoogle Scholar
  112. 112.
    Omran H, Fernandez C, Jung M, et al. Identification of a new gene locus for adolescent nephronophthisis, on chromosome 3q22 in a large Venezuelan pedigree. Am J Hum Genet. 2000;66(1):118–27.PubMedCentralPubMedGoogle Scholar
  113. 113.
    Otto E, Betz R, Rensing C, et al. A deletion distinct from the classical homologous recombination of juvenile nephronophthisis type 1 (NPH1) allows exact molecular definition of deletion breakpoints. Hum Mutat. 2000;16(3):211–23.PubMedGoogle Scholar
  114. 114.
    Otto E, Kispert A, Schatzle S, et al. Nephrocystin: gene expression and sequence conservation between human, mouse, and Caenorhabditis elegans. J Am Soc Nephrol. 2000;11(2):270–82.PubMedGoogle Scholar
  115. 115.
    Otto E, Hoefele J, Ruf R, et al. A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolution. Am J Hum Genet. 2002;71(5):1167–71.Google Scholar
  116. 116.
    Otto EA, Schermer B, Obara T, et al. Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination. Nat Genet. 2003;34(4):413–20.PubMedCentralPubMedGoogle Scholar
  117. 117.
    Otto EA, Loeys B, Khanna H, et al. Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin. Nat Genet. 2005;37(3):282–8.PubMedGoogle Scholar
  118. 118.
    Otto EA, Trapp ML, Schultheiss UT, et al. NEK8 mutations affect ciliary and centrosomal localization and may cause nephronophthisis. J Am Soc Nephrol. 2008;19(3):587–92.PubMedCentralPubMedGoogle Scholar
  119. 119.
    Parisi MA, Dobyns WB. Human malformations of the midbrain and hindbrain: review and proposed classification scheme. Mol Genet Metab. 2003;80(1–2):36–53.PubMedGoogle Scholar
  120. 120.
    Parisi MA, Doherty D, Eckert ML, et al. AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome. J Med Genet. 2006;43(4):334–9.PubMedCentralPubMedGoogle Scholar
  121. 121.
    Pazour GJ, Rosenbaum JL. Intraflagellar transport and cilia-dependent diseases. Trends Cell Biol. 2002;12(12):551–5.PubMedGoogle Scholar
  122. 122.
    Pazour GJ, Dickert BL, Witman GB. The DHC1b (DHC2) isoform of cytoplasmic dynein is required for flagellar assembly. J Cell Biol. 1999;144(3):473–81.PubMedCentralPubMedGoogle Scholar
  123. 123.
    Pazour GJ, Dickert BL, Vucica Y, et al. Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. J Cell Biol. 2000;151(3):709–18.PubMedCentralPubMedGoogle Scholar
  124. 124.
    Potter DE, Holliday MA, Piel CF, et al. Treatment of end-stage renal disease in children: a 15-year experience. Kidney Int. 1980;18(1):103–9.PubMedGoogle Scholar
  125. 125.
    Proesmans W, Van Damme B, Macken J. Nephronophthisis and tapetoretinal degeneration associated with liver fibrosis. Clin Nephrol. 1975;3(4):160–4.PubMedGoogle Scholar
  126. 126.
    Rayfield EJ, McDonald FD. Red and blonde hair in renal medullary cystic disease. Arch Intern Med. 1972;130(1):72–5.PubMedGoogle Scholar
  127. 127.
    Resnick J, Sisson S, Vernier RL. Tamm-Horsfall protein. Abnormal localization in renal disease. Lab Invest. 1978;38:550.PubMedGoogle Scholar
  128. 128.
    Rezende-Lima W, Parreira KS, Garcia-Gonzalez M, et al. Homozygosity for uromodulin disorders: FJHN and MCKD-type 2. Kidney Int. 2004;66(2):558–63.PubMedGoogle Scholar
  129. 129.
    Roepman R, Bernoud-Hubac N, Schick DE, et al. The retinitis pigmentosa gtpase regulator (RPGR) interacts with novel transport-like proteins in the outer segments of rod photoreceptors. Hum Mol Genet. 2000;9(14):2095–105.PubMedGoogle Scholar
  130. 130.
    Roume J, Genin E, Cormier-Daire V, et al. A gene for Meckel syndrome maps to chromosome 11q13. Am J Hum Genet. 1998;63(4):1095–101.PubMedCentralPubMedGoogle Scholar
  131. 131.
    Saadi-Kheddouci S, Berrebi D, Romagnolo B, et al. Early development of polycystic kidney disease in transgenic mice expressing an activated mutant of the beta-catenin gene. Oncogene. 2001;20(42):5972–81.PubMedGoogle Scholar
  132. 132.
    Saar K, Al-Gazali L, Sztriha L, et al. Homozygosity mapping in families with Joubert syndrome identifies a locus on chromosome 9q34.3 and evidence for genetic heterogeneity. Am J Hum Genet. 1999;65(6):1666–71.PubMedCentralPubMedGoogle Scholar
  133. 133.
    Sang L, Miller JJ, Corbit KC, Giles RH, Brauer MJ, Otto EA, Baye LM, Wen X, Scales SJ, Kwong M, Huntzicker EG, Sfakianos MK, Sandoval W, Bazan JF, Kulkarni P, Garcia-Gonzalo FR, Seol AD, O’Toole JF, Held S, Reutter HM, Lane WS, Rafiq MA, Noor A, Ansar M, Devi AR, Sheffield VC, Slusarski DC, Vincent JB, Doherty DA, Hildebrandt F, Reiter JF, Jackson PK. Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell. 2011;145(4):513–28.PubMedCentralPubMedGoogle Scholar
  134. 134.
    Saraiva JM, Baraitser M. Joubert syndrome: a review. Am J Med Genet. 1992;43(4):726–31.PubMedGoogle Scholar
  135. 135.
    Sarimurat N, Elcioglu N, Tekant GT, et al. Jeune’s asphyxiating thoracic dystrophy of the newborn. Eur J Pediatr Surg. 1998;8(2):100–1.PubMedGoogle Scholar
  136. 136.
    Satran D, Pierpont ME, Dobyns WB. Cerebello-oculo-renal syndromes including Arima, Senior-Loken and COACH syndromes: more than just variants of Joubert syndrome. Am J Med Genet. 1999;86(5):459–69.PubMedGoogle Scholar
  137. 137.
    Saunier S, Calado J, Heilig R, et al. A novel gene that encodes a protein with a putative src homology 3 domain is a candidate gene for familial juvenile nephronophthisis. Hum Mol Genet. 1997;6(13):2317–23.PubMedGoogle Scholar
  138. 138.
    Saunier S, Morin G, Calado J, et al. Large deletions of the NPH1 region in Cogan syndrome (CS) associated with familial juvenile nephronophthisis (NPH). Am J Hum Genet. 1997;61:A346.Google Scholar
  139. 139.
    Saunier S, Calado J, Benessy F, et al. Characterization of the NPHP1 locus: mutational mechanism involved in deletions in familial juvenile nephronophthisis. Am J Hum Genet. 2000;66(3):778–89.PubMedCentralPubMedGoogle Scholar
  140. 140.
    Sayer JA, Otto EA, O’Toole JF, et al. The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4. Nat Genet. 2006;38(6):674–81.PubMedGoogle Scholar
  141. 141.
    Schermer B, Hopker K, Omran H, et al. Phosphorylation by casein kinase 2 induces PACS-1 binding of nephrocystin and targeting to cilia. EMBO J. 2005;24(24):4415–24.PubMedCentralPubMedGoogle Scholar
  142. 142.
    Schuermann MJ, Otto E, Becker A, et al. Mapping of gene loci for nephronophthisis type 4 and Senior-Løken Syndrome, to chromosome 1p36. Am J Hum Genet. 2002;70(5):1240–6.PubMedCentralPubMedGoogle Scholar
  143. 143.
    Scolari F, Ghiggeri GM, Amoroso A, et al. Genetic heterogeneity for autosomal dominant medullary cystic kidney disease (ADMCKD). J Am Soc Nephrol. 1998;9:393A.Google Scholar
  144. 144.
    Scolari F, Puzzer D, Amoroso A, et al. Identification of a new locus for medullary cystic disease, on chromosome 16p12. Am J Hum Genet. 1999;64(6):1560–655.Google Scholar
  145. 145.
    Senior B, Friedmann AI, Braudo JL. Juvenile familial nephropathy with tapetoretinal degeneration: a new oculorenal dystrophy. Am J Ophthalmol. 1961;52:625–33.PubMedGoogle Scholar
  146. 146.
    Sherman FE, Studnicki FM, Fetterman GH. Renal lesions of familial juvenile nephronophthisis examined by microdissection. Am J Clin Pathol. 1971;55:391.PubMedGoogle Scholar
  147. 147.
    Simons M, Gloy J, Ganner A, et al. Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nat Genet. 2005;37(5):537–43.PubMedCentralPubMedGoogle Scholar
  148. 148.
    Smith C, Graham J. Congenital medullary cysts of the kidneys with severe refractory anemia. Am J Dis Child. 1945;69:369–77.Google Scholar
  149. 149.
    Smith UM, Consugar M, Tee LJ, et al. The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat. Nat Genet. 2006;38(2):191–6.PubMedGoogle Scholar
  150. 150.
    Sohara E, Luo Y, Zhang J, et al. Nek8 regulates the expression and localization of polycystin-1 and polycystin-2. J Am Soc Nephrol. 2008;19(3):469–76.PubMedCentralPubMedGoogle Scholar
  151. 151.
    Spurr NK, Barton H, Bashir R, et al. Report and abstracts of the third international workshop on human chromosome 2 mapping 1994. Aarhus, Denmark, June 24–26, 1994. Cytogenet Cell Genet. 1994;67(4):215–44.PubMedGoogle Scholar
  152. 152.
    Spurr NK, Bashir R, Bushby K, et al. Report and abstracts of the fourth international workshop on human chromosome 2 mapping 1996. Cytogenet Cell Genet. 1996;73(4):255–73.Google Scholar
  153. 153.
    Stavrou C, Koptides M, Tombazos C, et al. Autosomal-dominant medullary cystic kidney disease type 1: clinical and molecular findings in six large Cypriot families. Kidney Int. 2002;62(4):1385–94.PubMedGoogle Scholar
  154. 154.
    Steel BT, Lirenman DS, Battie CW. Nephronophthisis. Am J Med. 1980;68:531–8.Google Scholar
  155. 155.
    Sworn MJ, Eisinger AJ. Medullary cystic disease and juvenile nephronophthisis in separate members of the same family. Arch Dis Child. 1972;47:278.PubMedCentralPubMedGoogle Scholar
  156. 156.
    Torres VE, Wang X, Qian Q, et al. Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease. Nat Med. 2004;10(4):363–4.PubMedGoogle Scholar
  157. 157.
    Tsimaratos M, Sarles J, Sigaudy S, Philip N. Renal and retinal involvement in the Sensenbrenner syndrome. Am J Med Genet. 1998;77(4):337.PubMedGoogle Scholar
  158. 158.
    Utsch B, Sayer JA, Attanasio M, et al. Identification of the first AHI1 gene mutations in nephronophthisis-associated Joubert syndrome. Pediatr Nephrol. 2006;21(1):32–5.PubMedGoogle Scholar
  159. 159.
    Valente EM, Marsh SE, Castori M, et al. Distinguishing the four genetic causes of Jouberts syndrome-related disorders. Ann Neurol. 2005;57(4):513–9.PubMedGoogle Scholar
  160. 160.
    Valente EM, Silhavy JL, Brancati F, et al. Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropic forms of Joubert syndrome. Nat Genet. 2006;38(6):623–5.PubMedGoogle Scholar
  161. 161.
    van Collenburg JJ, Thompson MW, Huber J. Clinical, pathological and genetic aspects of a form of cystic disease of the renal medulla: familial juvenile nephronophthisis (FJN). Clin Nephrol. 1978;9(2):55–62.PubMedGoogle Scholar
  162. 162.
    Waldherr R. Der nephronophthise-komplex. Nieren- und Hochdruckkh. 1983;12:397–406.Google Scholar
  163. 163.
    Waldherr R, Lennert T, Weber HP, et al. The nephronophthisis complex. A clinicopathologic study in children. Virchows Arch A Pathol Anat Histol. 1982;394(3):235–54.PubMedGoogle Scholar
  164. 164.
    Watnick T, Germino G. From cilia to cyst. Nat Genet. 2003;34(4):355–6.PubMedGoogle Scholar
  165. 165.
    Winkelbauer ME, Schafer JC, Haycraft CJ, et al. The C. Elegans homologs of nephrocystin-1 and nephrocystin-4 are cilia transition zone proteins involved in chemosensory perception. J Cell Sci. 2005;118(Pt 23):5575–87.PubMedGoogle Scholar
  166. 166.
    Wolf MT, Karle SM, Schwarz S, Anlauf M, Anlauf M, Glaeser L, Kroiss S, Burton C, Feest T, Otto E, Fuchshuber A, Hildebrandt F. Refinement of the critical region for MCKD1 by detection of transcontinental haplotype sharing. Kidney Int. 2003;64(3):788–92.PubMedGoogle Scholar
  167. 167.
    Wolf MT, Mucha BE, Attanasio M, et al. Mutations of the Uromodulin gene in MCKD type 2 patients cluster in exon 4, which encodes three EGF-like domains. Kidney Int. 2003;64(5):1580–7.PubMedGoogle Scholar
  168. 168.
    Wolf MT, Lee J, Panther F, et al. Expression and phenotype analysis of the nephrocystin-1 and nephrocystin-4 homologs in Caenorhabditis elegans. J Am Soc Nephrol. 2005;16(3):676–87.PubMedGoogle Scholar
  169. 169.
    Wolf MT, Mucha BE, Hennies HC, et al. Medullary cystic kidney disease type 1: mutational analysis in 37 genes based on haplotype sharing. Hum Genet. 2006;119(6):649–58.PubMedGoogle Scholar
  170. 170.
    Wolf MT, Saunier S, O’Toole JF, et al. Mutational analysis of the RPGRIP1L gene in patients with Joubert syndrome and nephronophthisis. Kidney Int. 2007;72(12):1520–6.PubMedGoogle Scholar
  171. 171.
    Zhou W, Otto EA, Cluckey A, Airik R, Hurd TW, Chaki M, Diaz K, Lach FP, Bennett GR, Gee HY, Ghosh AK, Natarajan S, Thongthip S, Veturi U, Allen SJ, Janssen S, Ramaswami G, Dixon J, Burkhalter F, Spoendlin M, Moch H, Mihatsch MJ, Verine J, Reade R, Soliman H, Godin M, Kiss D, Monga G, Mazzucco G, Amann K, Artunc F, Newland RC, Wiech T, Zschiedrich S, Huber TB, Friedl A, Slaats GG, Joles JA, Goldschmeding R, Washburn J, Giles RH, Levy S, Smogorzewska A, Hildebrandt F. FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair. Nat Genet. 2012;44(8):910-5. doi:10.1038/ng.2347.PubMedCentralPubMedGoogle Scholar
  172. 172.
    Zollinger HU, Mihatsch MJ, Edefonti A, et al. Nephronophthisis (medullary cystic disease of the kidney). A study using electron microscopy, immunofluorescence, and a review of the morphological findings. Helv Paediatr Acta. 1980;35(6):509–30.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Harvard Medical SchoolBostonUSA

Personalised recommendations