Skip to main content
SpringerLink
Log in

Variations of type IV collagen-encoding genes in patients with histological diagnosis of focal segmental glomerulosclerosis

  • Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Focal segmental glomerulosclerosis (FSGS), an important cause of end-stage kidney disease (ESKD), covers a spectrum of clinicopathological syndromes sharing a common glomerular lesion, based on an injury of podocytes caused by diverse insults to glomeruli. Although it is well expressed in many reports that the term FSGS is not useful and applicable to a single disease, particularly in genetic studies, FSGS continues to be used as a single clinical diagnosis. Distinguishing genetic forms of FSGS is important for the treatment and overall prognosis because secondary forms of FSGS, produced by rare pathogenic variations in podocyte genes, are not good candidates for immunosuppressive treatment. Over the past decade, several next generation sequencing (NGS) methods have been used to investigate the patients with steroid resistance nephrotic syndrome (SRNS) or FSGS. Pathogenic variants in COL4A3, COL4A4, or COL4A5 genes have been frequently identified in patients with histologic diagnosis of FSGS. The contribution of these mostly heterozygous genetic variations in FSGS pathogenesis and the clinical course of patients with these variations have not been well characterized. This review emphasizes the importance of appropriate approach in selection and diagnosis of cases and interpretation of the genetic data in these studies and suggests a detailed review of existing clinical variant databases using newly available population genetic data.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Fogo AB (2015) Causes and pathogenesis of focal segmental glomerulosclerosis. Nat Rev Nephrol 11:76–87

    PubMed  CAS  Google Scholar 

  2. D’Agati VD, Kaskel FJ, Falk RJ (2011) Focal segmental glomerulosclerosis. N Engl J Med 365:2398–2411

    PubMed  Google Scholar 

  3. Benoit G, Machuca E, Antignac C (2010) Hereditary nephrotic syndrome: a systematic approach for genetic testing and a review of associated podocyte gene mutations. Pediatr Nephrol 25:1621–1632

    PubMed  PubMed Central  Google Scholar 

  4. Groopman EE, Rasouly HM, Gharavi AG (2018) Genomic medicine for kidney disease. Nat Rev Nephrol 14:83–104

    PubMed  PubMed Central  CAS  Google Scholar 

  5. Santín S, Bullich G, Tazón-Vega B, García-Maset R, Giménez I, Silva I, Ruíz P, Ballarín J, Torra R, Ars E (2011) Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 6:1139–1148

    PubMed  PubMed Central  Google Scholar 

  6. Bierzynska A, McCarthy HJ, Soderquest K, Sen ES, Colby E, Ding WY, Nabhan MM, Kerecuk L, Hegde S, Hughes D, Marks S, Feather S, Jones C, Webb NJ, Ognjanovic M, Christian M, Gilbert RD, Sinha MD, Lord GM, Simpson M, Koziell AB, Welsh GI, Saleem MA (2017) Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management. Kidney Int 91:937–947

    PubMed  Google Scholar 

  7. Sadowski CE, Lovric S, Ashraf S, Pabst WL, Gee HY, Kohl S, Engelmann S, Vega-Warner V, Fang H, Halbritter J, Somers MJ, Tan W, Shril S, Fessi I, Lifton RP, Bockenhauer D, El-Desoky S, Kari JA, Zenker M, Kemper MJ, Mueller D, Fathy HM, Soliman NA, SRNS Study Group, Hildebrandt F (2015) A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol 26:1279–1289

    PubMed  CAS  Google Scholar 

  8. Wang F, Zhang Y, Mao J, Yu Z, Yi Z, Yu L, Sun J, Wei X, Ding F, Zhang H, Xiao H, Yao Y, TanW LS, Ding J, Hildebrandt F (2017) Spectrum of mutations in Chinese children with steroidresistant nephrotic syndrome. Pediatr Nephrol 32:1181–1192

    PubMed  PubMed Central  Google Scholar 

  9. Trautmann A, Bodria M, Ozaltin F, Gheisari A, Melk A, Azocar M, Anarat A, Caliskan S, Emma F, Gellermann J, Oh J, Baskin E, Ksiazek J, Remuzzi G, Erdogan O, Akman S, Dusek J, Davitaia T, Özkaya O, Papachristou F, Firszt-Adamczyk A, Urasinski T, Testa S, Krmar RT, Hyla-Klekot L, Pasini A, Özcakar ZB, Sallay P, Cakar N, Galanti M, Terzic J, Aoun B, Caldas Afonso A, Szymanik-Grzelak H, Lipska BS, Schnaidt S, Schaefer F, Podo-Net Consortium (2015) Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort. Clin J Am Soc Nephrol 10:592–600

    PubMed  PubMed Central  Google Scholar 

  10. De Vriese AS, Sethi S, Nath KA, Glassock RJ, Fervenza FC (2018) Differentiating primary, genetic, and secondary FSGS in adults: a clinicopathologic approach. J Am Soc Nephrol 29:759–774

    PubMed  PubMed Central  Google Scholar 

  11. Voskarides K, Damianou L, Neocleous V, Zouvani I, Christodoulidou S, Hadjiconstantinou V, Ioannou K, Athanasiou Y, Patsias C, Alexopoulos E, Pierides A, Kyriacou K, Deltas C (2007) COL4A3/COL4A4 mutations producing focal segmental glomerulosclerosis and renal failure in thin basement membrane nephropathy. J Am Soc Nephrol 18:3004–3016

    PubMed  CAS  Google Scholar 

  12. McCarthy HJ, Bierzynska A, Wherlock M, Ognjanovic M, Kerecuk L, Hegde S, Feather S, Gilbert RD, Krischock L, Jones C, Sinha MD, Webb NJ, Christian M, Williams MM, Marks S, Koziell A, Welsh GI, Saleem MA, RADAR the UK SRNS Study Group (2013) Simultaneous sequencing of 24 genes associated with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 8:637–648

    PubMed  PubMed Central  CAS  Google Scholar 

  13. Gibson J, Gilbert RD, Bunyan DJ, Angus EM, Fowler DJ, Ennis S (2013) Exome analysis resolves differential diagnosis of familial kidney disease and uncovers a potential confounding variant. Genet Res (Camb) 95:165–173

    CAS  Google Scholar 

  14. Malone, Phelan PJ, Hall G, Cetincelik U, Homstad A, Alonso AS, Jiang R, Lindsey TB, Wu G, Sparks MA, Smith SR, Webb NJ, Kalra PA, Adeyemo AA, Shaw AS, Conlon PJ, Jennette JC, Howell DN, Winn MP, Gbadegesin RA (2014) Rare hereditary COL4A3/COL4A4 variants may be mistaken for familial focal segmental glomerulosclerosis. Kidney Int 86:1253–1259

    PubMed  PubMed Central  CAS  Google Scholar 

  15. Xie J, Wu X, Ren H, Wang W, Wang Z, Pan X, Hao X, Tong J, Ma J, Ye Z, Meng G, Zhu Y, Kiryluk K, Kong X, Hu L, Chen N (2014) COL4A3 mutations cause focal segmental glomerulosclerosis. J Mol Cell Biol 6:498–505

    PubMed  CAS  Google Scholar 

  16. Bullich G, Trujillano D, Santín S, Ossowski S, Mendizábal S, Fraga G, Madrid Á, Ariceta G, Ballarín J, Torra R, Estivill X, Ars E (2015) Targeted next-generation sequencing in steroid-resistant nephrotic syndrome: mutations in multiple glomerular genes may influence disease severity. Eur J Hum Genet 23:1192–1199

    PubMed  CAS  Google Scholar 

  17. Gast C, Pengelly RJ, Lyon M, Bunyan DJ, Seaby EG, Graham N, Venkat-Raman G, Ennis S (2016) Collagen (COL4A) mutations are the most frequent mutations underlying adult focal segmental glomerulosclerosis. Nephrol Dial Transplant 31:961–970

    PubMed  CAS  Google Scholar 

  18. Hines SL, Agarwal A, Ghandour M, Nabeel A, Mohammad AN, Atwal PS (2018) Novel variants in COL4A4 and COL4A5 are rare causes of FSGS in two unrelated families. Hum Genome Var 5:15. https://doi.org/10.1038/s41439-018-0016-8eCollection 2018

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Gribouval O, Boyer O, Hummel A, Dantal J, Martinez F, Sberro-Soussan R, Etienne I, Chauveau D, Delahousse M, Lionet A, Allard J, Pouteil Noble C, Tête MJ, Heidet L, Antignac C, Servais A (2018) Identification of genetic causes for sporadic steroid-resistant nephrotic syndrome in adults. Kidney Int 94:1013–1022

    PubMed  CAS  Google Scholar 

  20. Varner JD, Chryst-Stangl M, Esezobor CI, Solarin A, Wu G, Lane B, Hall G, Abeyagunawardena A, Matory A, Hunley TE, Lin JJ, Howell D, Gbadegesin R (2018) Genetic testing for steroid-resistant-nephrotic syndrome in an outbred population. Front Pediatr 6:307. https://doi.org/10.3389/fped.2018.00307 eCollection 2018

    Article  PubMed  PubMed Central  Google Scholar 

  21. Yao T, Udwan K, John R, Rana A, Haghighi A, Xu L, Hack S, Reich HN, Hladunewich MA, Cattran DC, Paterson AD, Pei Y, Barua M (2019) Integration of genetic testing and pathology for the diagnosis of adults with FSGS. Clin J Am Soc Nephrol. https://doi.org/10.2215/CJN.08750718

  22. Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE, Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee (2008) ACMG recommendations for standards for interpretation and reporting of sequence variations. Revisions 2007. Genet Med 10:294–300

    PubMed  CAS  Google Scholar 

  23. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, ACMG Laboratory Quality Assurance Committee (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405–424

    PubMed  PubMed Central  Google Scholar 

  24. Voskarides K, Pierides A, Deltas C (2008) COL4A3/COL4A4 mutations link familial hematuria and focal segmental glomerulosclerosis. Glomerular epithelium destruction via basement membrane thinning? Connect Tissue Res 49(3):283–288

    PubMed  CAS  Google Scholar 

  25. Papazachariou L, Demosthenous P, Pieri M, Papagregoriou G, Savva I, Stavrou C, Zavros M, Athanasiou Y, Ioannou K, Patsias C, Panagides A, Potamitis C, Demetriou K, Prikis M, Hadjigavriel M, Kkolou M, Loukaidou P, Pastelli A, Michael A, Lazarou A, Arsali M, Damianou L, Goutziamani I, Soloukides A, Yioukas L, Elia A, Zouvani I, Polycarpou P, Pierides A, Voskarides K, Deltas C (2014) Frequency of COL4A3/COL4A4 mutations amongst families segregating glomerular microscopic hematuria and evidence for activation of the unfolded protein response. Focal and segmental glomerulosclerosis is a frequent development during ageing. PLoS One 9(12):e115015. https://doi.org/10.1371/journal.pone.0115015

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Papazachariou L, Papagregoriou G, Hadjipanagi D, Demosthenous P, Voskarides K, Koutsofti C, Stylianou K, Ioannou P, Xydakis D, Tzanakis I, Papadaki A, Kallivretakis N, Nikolakakis N, Perysinaki G, Gale DP, Diamantopoulos A, Goudas P, Goumenos D, Soloukides A, Boletis I, Melexopoulou C, Georgaki E, Frysira E, Komianou F, Grekas D, Paliouras C, Alivanis P, Vergoulas G, Pierides A, Daphnis E, Deltas C (2017) Frequent COL4 mutations in familial microhematuria accompanied by later-onset Alport nephropathy due to focal segmental glomerulosclerosis. Clin Genet 92(5):517–527

    PubMed  CAS  Google Scholar 

  27. 1000 Genomes Project Consortium, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR (2015) A global reference for human genetic variation. Nature 526:68–74

    Google Scholar 

  28. Miner JH (2014) Pathology vs. molecular genetics: (re)defining the spectrum of Alport syndrome. Kidney Int 86:1081–1083

    PubMed  PubMed Central  CAS  Google Scholar 

  29. Pierides A, Voskarides K, Athanasiou Y, Ioannou K, Damianou L, Arsali M, Zavros M, Pierides M, Vargemezis V, Patsias C, Zouvani I, Elia A, Kyriacou K, Deltas C (2009) Clinico-pathological correlations in 127 patients in 11 large pedigrees, segregating one of three heterozygous mutations in the COL4A3/ COL4A4 genes associated with familial haematuria and significant late progression to proteinuria and chronic kidney disease from focal segmental glomerulosclerosis. Nephrol Dial Transplant 24:2721–2729

    PubMed  CAS  Google Scholar 

  30. Abrahamson DR, Hudson BG, Stroganova L, Borza DB, St John PL (2009) Cellular origins of type IV collagen networks in developing glomeruli. J Am Soc Nephrol 20:1471–1479

    PubMed  PubMed Central  CAS  Google Scholar 

  31. Rajpar MH, McDermott B, Kung L, Eardley R, Knowles L, Heeran M, Thornton DJ, Wilson R, Bateman JF, Poulsom R, Arvan P, Kadler KE, Briggs MD, Boot-Handford RP (2009) Targeted induction of endoplasmic reticulum stress induces cartilage pathology. PLoS Genet 5:e1000691. https://doi.org/10.1371/journal.pgen.1000691

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Pieri M, Stefanou C, Zaravinos A, Erguler K, Stylianou K, Lapathitis G, Karaiskos C, Savva I, Paraskeva R, Dweep H, Sticht C, Anastasiadou N, Zouvani I, Goumenos D, Felekkis K, Saleem M, Voskarides K, Gretz N, Deltas C (2014) Evidence for activation of the unfolded protein response in collagen IV nephropathies. J Am Soc Nephrol 25(2):260–275

    PubMed  CAS  Google Scholar 

  33. Kobayashi T, Kakihara T, Uchiyama M (2008) Mutational analysis of type IV collagen alpha5 chain, with respect to heterotrimer formation. Biochem Biophys Res Commun 366:60–65

    PubMed  CAS  Google Scholar 

  34. Kobayashi T, Uchiyama M (2003) Characterization of assembly of recombinant type IV collagen alpha3, alpha4, and alpha5 chains in transfected cell strains. Kidney Int 64:1986–1996

    PubMed  CAS  Google Scholar 

  35. Kobayashi T, Uchiyama M (2010) Mutant-type alpha5(IV) collagen in a mild form of Alport syndrome has residual ability to form a heterotrimer. Pediatr Nephrol 25:1169–1172

    PubMed  Google Scholar 

  36. Goldstein DB, Allen A, Keebler J, Margulies EH, Petrou S, Petrovski S, Sunyaev S (2013) Sequencing studies in human genetics: design and interpretation. Nat Rev Genet 14:460–470

    PubMed  PubMed Central  CAS  Google Scholar 

  37. Lovric S, Ashraf S, Tan W, Hildebrandt F (2016) Genetic testing in steroid-resistant nephrotic syndrome: when and how? Nephrol Dial Transplant 31:1802–1813

    PubMed  CAS  Google Scholar 

  38. Bose B, Cattran D (2014) Glomerular diseases: FSGS. Clin J Am Soc Nephrol 9:626–632

    PubMed  Google Scholar 

  39. Howie AJ. (2018) Genetic studies of focal segmental glomerulosclerosis: a waste of scientific time? Pediatr Nephrol. Dec 27. https://doi.org/10.1007/s00467-018-4161-6.

  40. Howie AJ (2011) Problems with ‘focal segmental glomerulosclerosis. Pediatr Nephrol 26:1197–1205

    PubMed  Google Scholar 

  41. D’Agati V (1994) The many masks of focal segmental glomerulosclerosis. Kidney Int 46:1223–1241

    PubMed  Google Scholar 

  42. Kambham N, Markowitz GS, Valeri AM, Lin J, D’Agati VD (2001) Obesity-related glomerulopathy: an emerging epidemic. Kidney Int 59:1498–1509

    PubMed  CAS  Google Scholar 

  43. Hommos MS, De Vriese AS, Alexander MP, Sethi S, Vaughan L, Zand L, Bharucha K, Lepori N, Rule AD, Fervenza FC (2017) The incidence of primary vs secondary focal segmental glomerulosclerosis: a clinicopathologic study. Mayo Clin Proc 92:1772–1781

    PubMed  PubMed Central  Google Scholar 

  44. Henderson JM, Alexander MP, Pollak MR (2009) Patients with ACTN4 mutations demonstrate distinctive features of glomerular injury. J Am Soc Nephrol 20:961–968

    PubMed  PubMed Central  CAS  Google Scholar 

  45. Yu H, Artomov M, Brähler S, Stander MC, Shamsan G, Sampson MG, White JM, Kretzler M, Miner JH, Jain S, Winkler CA, Mitra RD, Kopp JB, Daly MJ, Shaw AS (2016) A role for genetic susceptibility in sporadic focal segmental glomerulosclerosis. J Clin Invest 126:1067–1078

    PubMed  PubMed Central  Google Scholar 

  46. Choi HJ, Lee BH, Cho HY, Moon KC, Ha IS, Nagata M, Choi Y, Cheong HI (2008) Familial focal segmental glomerulosclerosis associated with an ACTN4 mutation and paternal germline mosaicism. Am J Kidney Dis 51:834–838

    PubMed  CAS  Google Scholar 

  47. D’Agati VD (2003) Pathologic classification of focal segmental glomerulosclerosis. Sem Nephrol 23:117–134

    Google Scholar 

  48. D’Agati VD, Alster JM, Jennette JC, Thomas DB, Pullman J, Savino DA, Cohen AH, Gipson DS, Gassman JJ, Radeva MK, Moxey-Mims MM, Friedman AL, Kaskel FJ, Trachtman H, Alpers CE, Fogo AB, Greene TH, Nast CC (2013) Association of histologic variants in FSGS clinical trial with presenting features and outcomes. Clin J Am Soc Nephrol 8:399–406

    PubMed  Google Scholar 

  49. Kashtan CE, Ding J, Garosi G, Heidet L, Massella L, Nakanishi K, Nozu K, Renieri A, Rheault M, Wang F, Gross O (2018) Alport syndrome: a unified classification of genetic disorders of collagen IV α345: a position paper of the Alport Syndrome Classification Working Group. Kidney Int 93:1045–1051

    PubMed  Google Scholar 

  50. Haas M (2009) Alport syndrome and thin glomerular basement membrane nephropathy: a practical approach to diagnosis. Arch Pathol Lab Med 133:224–232

    PubMed  Google Scholar 

  51. Wickman L, Hodgin JB, Wang SQ, Afshinnia F, Kershaw D, Wiggins RC (2016) Podocyte depletion in thin GBM and Alport syndrome. PLoS One 11:e0155255. https://doi.org/10.1371/journal.pone.0155255

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Yao XD, Chen X, Huang GY, Yu YT, Xu ST, Hu YL, Wang QW, Chen HP, Zeng CH, Ji DX, Hu WX, Tang Z, Liu ZH (2012) Challenge in pathologic diagnosis of Alport syndrome: evidence from correction of previous misdiagnosis. Orphanet J Rare Dis 7:100

    PubMed  PubMed Central  Google Scholar 

  53. Said SM, Fidler ME, Valeri AM, McCann B, Fiedler W, Cornell LD, Alexander MP, Alkhunaizi AM, Sullivan A, Cramer CH, Hogan MC, Nasr SH (2016) Negative staining for COL4A5 correlates with worse prognosis and more severe ultrastructural alterations in males with Alport syndrome. Kidney Int Rep 2:44–52

    PubMed  PubMed Central  Google Scholar 

  54. Deltas C, Savva I, Voskarides K, Papazachariou L, Pierides A (2015) Carriers of autosomal recessive Alport syndrome with thin basement membrane nephropathy presenting as focal segmental glomerulosclerosis in later life. Nephron 130:271–280

    PubMed  CAS  Google Scholar 

  55. Longo I, Porcedda P, Mari F, Giachino D, Meloni I, Deplano C, Brusco A, Bosio M, Massella L, Lavoratti G, Roccatello D, Frascá G, Mazzucco G, Muda AO, Conti M, Fasciolo F, Arrondel C, Heidet L, Renieri A, De Marchi M (2002) COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome. Kidney Int 61:1947–1956

    PubMed  CAS  Google Scholar 

  56. Tonna S, Wang YY, Wilson D, Rigby L, Tabone T, Cotton R, Savige J (2008) The R229Q mutation in NPHS2 may predispose to proteinuria in thin-basement-membrane nephropathy. Pediatr Nephrol 23:2201–2207

    PubMed  Google Scholar 

  57. Voskarides K, Arsali M, Athanasiou Y, Elia A, Pierides A, Deltas C (2012) Evidence that NPHS2-R 229Q pre-disposes to proteinuria and renal failure in familial hematuria. Pediatr Nephrol 27(4):675–679

    PubMed  Google Scholar 

  58. Voskarides K, Stefanou C, Pieri M, Demosthenous P, Felekkis K, Arsali M, Athanasiou Y, Xydakis D, Stylianou K, Daphnis E, Goulielmos G, Loizou P, Savige J, Höhne M, Völker LA, Benzing T, Maxwell PH, Gale DP, Gorski M, Böger C, Kollerits B, Kronenberg F, Paulweber B, Zavros M, Pierides A, Deltas C (2017) A functional variant in NEPH3 gene confers high risk of renal failure in primary hematuric glomerulopathies. Evidence for predisposition to microalbuminuria in the general population. PLoS One 12(3):e0174274. https://doi.org/10.1371/journal.pone.0174274

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Savige J, Ariani F, Mari F, Bruttini M, Renieri A, Gross O, Deltas C, Flinter F, Ding J, Gale DP, Nagel M, Yau M, Shagam L, Torra R, Ars E, Hoefele J, Garosi G, Storey H (2018) Expert consensus guidelines for the genetic diagnosis of Alport syndrome. Pediatr Nephrol. https://doi.org/10.1007/s00467-018-3985-4

  60. Fallerini C, Baldassarri M, Trevisson E, Morbidoni V, La Manna A, Lazzarin R, Pasini A, Barbano G, Pinciaroli AR, Garosi G, Frullanti E, Pinto AM, Mencarelli MA, Mari F, Renieri A, Ariani F (2017) Alport syndrome: impact of digenic inheritance in patients management. Clin Genet 92:34–44

    PubMed  CAS  Google Scholar 

  61. Mencarelli MA, Heidet L, Storey H, van Geel M, Knebelmann B, Fallerini C, Miglietti N, Antonucci MF, Cetta F, Sayer JA, van den Wijngaard A, Yau S, Mari F, BruttiniM AF, Dahan K, Smeets B, Antignac C, Flinter F, Renieri A (2015) Evidence of digenic inheritance in Alport syndrome. J Med Genet 52:163–174

    PubMed  CAS  Google Scholar 

  62. Mohammad M, Nanra R, Colville D, Trevillian P, Wang Y, Storey H, Flinter F, Savige J (2014) A female with X-linked Alport syndrome and compound heterozygous COL4A5 mutations. Pediatr Nephrol 29:481–485

    PubMed  Google Scholar 

  63. Lennon R, Stuart HM, Bierzynska A, RandlesMJ KB, Hillman KA, Batra G, Campbell J, Storey H, Flinter FA, Koziell A, Welsh GI, Saleem MA, Webb NJ, Woolf AS (2015) Coinheritance of COL4A5 and MYO1E mutations accentuate the severity of kidney disease. Pediatr Nephrol 30:1459–1465

    PubMed  PubMed Central  Google Scholar 

  64. Bullich G, Trujillano D, Santin S, Ossowski S, Mendizabal S, Fraga G, Madrid A, Ariceta G, Ballarin J, Torra R, Estivill X, Ars E (2015) Targeted next-generation sequencing in steroid-resistant nephrotic syndrome: mutations in multiple glomerular genes may nfluence disease severity. Eur J Hum Genet 23:1192–1199

    PubMed  CAS  Google Scholar 

  65. Voskarides K, Papagregoriou G, Hadjipanagi D, Petrou I, Savva I, Elia A, Athanasiou Y, Pastelli A, Kkolou M, Hadjigavriel M, Stavrou C, Pierides A, Deltas C (2018) COL4A5 and LAMA5 variants co-inherited in familial hematuria: digenic inheritance or genetic modifier effect? BMC Nephrol 19(1):114. https://doi.org/10.1186/s12882-018-0906-5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Shah N, Hou YC, Yu HC, Sainger R, Caskey CT, Venter JC, Telenti A (2018) Identification of misclassified ClinVar variants via disease population prevalence. Am J Hum Genet 102:609–619

    PubMed  PubMed Central  CAS  Google Scholar 

  67. Groopman EE, Marasa M, Cameron-Christie S, Petrovski S, Aggarwal VS, Milo-Rasouly H, Li Y, Zhang J, Nestor J, Krithivasan P, Lam WY, Mitrotti A, Piva S, Kil BH, Chatterjee D, Reingold R, Bradbury D, DiVecchia M, Snyder H, Mu X, Mehl K, Balderes O, Fasel DA, Weng C, Radhakrishnan J, Canetta P, Appel GB, Bomback AS, Ahn W, Uy NS, Alam S, Cohen DJ, Crew RJ, Dube GK, Rao MK, Kamalakaran S, Copeland B, Ren Z, Bridgers J, Malone CD, Mebane CM, Dagaonkar N, Fellström BC, Haefliger C, Mohan S, Sanna-Cherchi S, Kiryluk K, Fleckner J, March R, Platt A, Goldstein DB, Gharavi AG (2019) Diagnostic utility of exome sequencing for kidney disease. N Engl J Med 380:142–151

    PubMed  CAS  Google Scholar 

  68. Manolio TA, Fowler DM, Starita LM, Haendel MA, MacArthur DG, Biesecker LG, Worthey E, Chisholm RL, Green ED, Jacob HJ, McLeod HL, Roden D, Rodriguez LL, Williams MS, Cooper GM, Cox NJ, Herman GE, Kingsmore S, Lo C, Lutz C, MacRae CA, Nussbaum RL, Ordovas JM, Ramos EM, Robinson PN, Rubinstein WS, Seidman C, Stranger BE, Wang H, Westerfield M, Bult C (2017) Bedside back to bench: building bridges between basic and clinical genomic research. Cell 169:6–12

    PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, Istanbul School of Medicine, Istanbul University, Capa, Fatih, 34093, Istanbul, Turkey

    Erol Demir & Yasar Caliskan

Authors
  1. Erol Demir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasar Caliskan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasar Caliskan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Demir, E., Caliskan, Y. Variations of type IV collagen-encoding genes in patients with histological diagnosis of focal segmental glomerulosclerosis. Pediatr Nephrol 35, 927–936 (2020). https://doi.org/10.1007/s00467-019-04282-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-019-04282-y

Keywords

Search

Navigation