hereditary nephritis

Summary

Summary: A group of inherited conditions characterized initially by HEMATURIA and slowly progressing to RENAL INSUFFICIENCY. The most common form is the Alport syndrome (hereditary nephritis with HEARING LOSS) which is caused by mutations in genes for TYPE IV COLLAGEN and defective GLOMERULAR BASEMENT MEMBRANE.

Top Publications

  1. Mochizuki T, Lemmink H, Mariyama M, Antignac C, Gubler M, Pirson Y, et al. Identification of mutations in the alpha 3(IV) and alpha 4(IV) collagen genes in autosomal recessive Alport syndrome. Nat Genet. 1994;8:77-81 pubmed
  2. Hudson B, Tryggvason K, Sundaramoorthy M, Neilson E. Alport's syndrome, Goodpasture's syndrome, and type IV collagen. N Engl J Med. 2003;348:2543-56 pubmed
  3. Andrews K, Mudd J, Li C, Miner J. Quantitative trait loci influence renal disease progression in a mouse model of Alport syndrome. Am J Pathol. 2002;160:721-30 pubmed
    ..Analysis with Map Manager QT revealed QTLs linked to markers on chromosomes 9 and 16. A more detailed understanding of how these QTLs act could lead to new approaches for therapy in diverse renal diseases...
  4. Barker D, Denison J, Atkin C, Gregory M. Efficient detection of Alport syndrome COL4A5 mutations with multiplex genomic PCR-SSCP. Am J Med Genet. 2001;98:148-60 pubmed
    ..One of the 29 different mutations detected initially seemed to be a missense change in exon 32 but was found to cause exon skipping. Another missense variant may mark a novel functional site located in the collagenous domain...
  5. Kashtan C. Animal models of Alport syndrome. Nephrol Dial Transplant. 2002;17:1359-62 pubmed
  6. Harvey S, Zheng K, Jefferson B, Moak P, Sado Y, Naito I, et al. Transfer of the alpha 5(IV) collagen chain gene to smooth muscle restores in vivo expression of the alpha 6(IV) collagen chain in a canine model of Alport syndrome. Am J Pathol. 2003;162:873-85 pubmed
    ..This vector will serve as a useful tool to further explore gene therapy for Alport syndrome...
  7. Rao V, Lees G, Kashtan C, Nemori R, Singh R, Meehan D, et al. Increased expression of MMP-2, MMP-9 (type IV collagenases/gelatinases), and MT1-MMP in canine X-linked Alport syndrome (XLAS). Kidney Int. 2003;63:1736-48 pubmed
    ..In this study, a well-characterized naturally occurring canine model was employed to demonstrate a potential role for matrix metalloproteinases (MMPs) in Alport renal disease pathogenesis...
  8. Miner J, Sanes J. Molecular and functional defects in kidneys of mice lacking collagen alpha 3(IV): implications for Alport syndrome. J Cell Biol. 1996;135:1403-13 pubmed
    ..We suggest that these alterations contribute, along with loss of collagen IV isoforms per se, to renal pathology...
  9. Barker D, Pruchno C, Jiang X, Atkin C, Stone E, Denison J, et al. A mutation causing Alport syndrome with tardive hearing loss is common in the western United States. Am J Hum Genet. 1996;58:1157-65 pubmed
    ..Renal failure in an L1649R male typically occurs in the 4th or 5th decade and precedes the onset of significant hearing loss by approximately 10 years...

More Information

Publications62

  1. Zheng K, Thorner P, Marrano P, Baumal R, McInnes R. Canine X chromosome-linked hereditary nephritis: a genetic model for human X-linked hereditary nephritis resulting from a single base mutation in the gene encoding the alpha 5 chain of collagen type IV. Proc Natl Acad Sci U S A. 1994;91:3989-93 pubmed
    Many families with X-chromosome linked hereditary nephritis (HN) have mutations in the gene on the X chromosome that codes for the alpha 5 chain of collagen type IV. Canine X-linked HN is an animal model for human X-linked HN...
  2. Lemmink H, Mochizuki T, van den Heuvel L, Schroder C, Barrientos A, Monnens L, et al. Mutations in the type IV collagen alpha 3 (COL4A3) gene in autosomal recessive Alport syndrome. Hum Mol Genet. 1994;3:1269-73 pubmed
    ..It is concluded that COL4A3 is a major gene in the genetically and clinically heterogeneous Alport syndrome...
  3. Cox M, Lees G, Kashtan C, Murphy K. Genetic cause of X-linked Alport syndrome in a family of domestic dogs. Mamm Genome. 2003;14:396-403 pubmed
    ..Characterization of the causative mutation was followed by development of an allele-specific test for identification of dogs in this kindred that are destined to develop XLAS...
  4. Jais J, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, et al. X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: a "European Community Alport Syndrome Concerted Action" study. J Am Soc Nephrol. 2003;14:2603-10 pubmed
    ..Risk factors for developing renal failure have been identified: the occurrence and progressive increase in proteinuria, and the development of a hearing defect...
  5. Rheault M, Kren S, Thielen B, Mesa H, Crosson J, Thomas W, et al. Mouse model of X-linked Alport syndrome. J Am Soc Nephrol. 2004;15:1466-74 pubmed
    ..With alpha5(IV) expression reflecting X-inactivation patterns, it will be especially useful in studying determinants of disease variability in the carrier state...
  6. Kashtan C. Familial hematuria due to type IV collagen mutations: Alport syndrome and thin basement membrane nephropathy. Curr Opin Pediatr. 2004;16:177-81 pubmed
    ..This review will discuss the implications of these findings for the diagnosis and management of persistent glomerular hematuria...
  7. Rodgers K, Rao V, Meehan D, Fager N, Gotwals P, Ryan S, et al. Monocytes may promote myofibroblast accumulation and apoptosis in Alport renal fibrosis. Kidney Int. 2003;63:1338-55 pubmed
    ..While much has been done to explore the role of these cell types individually in fibrosis, the interactive dependency of monocytes and myofibroblasts has been only marginally explored...
  8. Chen D, Jefferson B, Harvey S, Zheng K, Gartley C, Jacobs R, et al. Cyclosporine a slows the progressive renal disease of alport syndrome (X-linked hereditary nephritis): results from a canine model. J Am Soc Nephrol. 2003;14:690-8 pubmed
    ..At least part of this beneficial effect comes from a delayed deterioration of GBM structure, which in turn may be related to glomerular hemodynamics altered by cyclosporine A...
  9. Gross O, Netzer K, Lambrecht R, Seibold S, Weber M. Meta-analysis of genotype-phenotype correlation in X-linked Alport syndrome: impact on clinical counselling. Nephrol Dial Transplant. 2002;17:1218-27 pubmed
    ..The goal of the present study was to identify the genotype-phenotype correlations that are helpful in clinical counseling. COL4A5-mutations (n=267) in males were analysed including 23 German Alport families...
  10. Heikkila P, Tibell A, Morita T, Chen Y, Wu G, Sado Y, et al. Adenovirus-mediated transfer of type IV collagen alpha5 chain cDNA into swine kidney in vivo: deposition of the protein into the glomerular basement membrane. Gene Ther. 2001;8:882-90 pubmed
    Gene therapy of Alport syndrome (hereditary nephritis) aims at the transfer of a corrected type IV collagen alpha chain gene into renal glomerular cells responsible for production of the glomerular basement membrane (GBM)...
  11. Barker D, Hostikka S, Zhou J, Chow L, Oliphant A, Gerken S, et al. Identification of mutations in the COL4A5 collagen gene in Alport syndrome. Science. 1990;248:1224-7 pubmed
  12. Barker D, Denison J, Atkin C, Gregory M. Common ancestry of three Ashkenazi-American families with Alport syndrome and COL4A5 R1677Q. Hum Genet. 1997;99:681-4 pubmed
    ..Ashkenazi-American families, causes a relatively mild form of nephritis with typical onset in the fourth or fifth decade, and may be involved in the etiology of a large proportion of adult-onset hereditary nephritis in Ashkenazi Jews.
  13. Martin P, Heiskari N, Zhou J, Leinonen A, Tumelius T, Hertz J, et al. High mutation detection rate in the COL4A5 collagen gene in suspected Alport syndrome using PCR and direct DNA sequencing. J Am Soc Nephrol. 1998;9:2291-301 pubmed
    Approximately 85% of patients with Alport syndrome (hereditary nephritis) have been estimated to have mutations in the X chromosomal COL4A5 collagen gene; the remaining cases are autosomal with mutations in the COL4A3 or COL4A4 genes ..
  14. Sayers R, Kalluri R, Rodgers K, Shield C, Meehan D, Cosgrove D. Role for transforming growth factor-beta1 in alport renal disease progression. Kidney Int. 1999;56:1662-73 pubmed
    ..In this study, the model was exploited to demonstrate a potential role for transforming growth factor-beta1 (TGF-beta1) in Alport renal disease pathogenesis...
  15. Cosgrove D, Rodgers K, Meehan D, Miller C, Bovard K, Gilroy A, et al. Integrin alpha1beta1 and transforming growth factor-beta1 play distinct roles in alport glomerular pathogenesis and serve as dual targets for metabolic therapy. Am J Pathol. 2000;157:1649-59 pubmed
    ..These data suggest that integrin alpha1beta1 and TGF-beta1 may provide useful targets for a dual therapy aimed at slowing disease progression in Alport glomerulonephritis...
  16. Andrews K, Betsuyaku T, Rogers S, Shipley J, Senior R, Miner J. Gelatinase B (MMP-9) is not essential in the normal kidney and does not influence progression of renal disease in a mouse model of Alport syndrome. Am J Pathol. 2000;157:303-11 pubmed
    ..Thus, gelB does not have a discernible role in the normal kidney and gelB is not involved in the progression of glomerulonephritis in a mouse model of Alport syndrome...
  17. Wilson J, Yoon H, Walker R, Eccles M. A novel Cys1638Tyr NC1 domain substitution in alpha5(IV) collagen causes Alport syndrome with late onset renal failure without hearing loss or eye abnormalities. Nephrol Dial Transplant. 2007;22:1338-46 pubmed
    ..More than 300 sequence variants in type IV collagen have been identified, including alterations in the non-collagenous NC1 domain...
  18. Cosgrove D, Meehan D, Grunkemeyer J, Kornak J, Sayers R, Hunter W, et al. Collagen COL4A3 knockout: a mouse model for autosomal Alport syndrome. Genes Dev. 1996;10:2981-92 pubmed
    ..Thus, expression of these basement membrane-associated proteins may be involved in the progression of Alport renal disease pathogenesis. The levels of mRNAs encoding the basement membrane-associated proteins at 7 weeks were unchanged...
  19. Longo I, Porcedda P, Mari F, Giachino D, Meloni I, Deplano C, et al. COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome. Kidney Int. 2002;61:1947-56 pubmed
    ..COL4A3/COL4A4 mutations: From familial hematuria to autosomal-dominant or recessive Alport syndrome...
  20. Matsushita T, Hayashi H, Kunishima S, Hayashi M, Ikejiri M, Takeshita K, et al. Targeted disruption of mouse ortholog of the human MYH9 responsible for macrothrombocytopenia with different organ involvement: hematological, nephrological, and otological studies of heterozygous KO mice. Biochem Biophys Res Commun. 2004;325:1163-71 pubmed
    ..Such observation may parallel the diverse expression of Alport's manifestations of human individuals with MYH9 disorders and suggest the limited requirement of the gene for maintenance and function of specific organs...
  21. Savige J, Rana K, Tonna S, Buzza M, Dagher H, Wang Y. Thin basement membrane nephropathy. Kidney Int. 2003;64:1169-78 pubmed
    ..Technical difficulties in the demonstration and interpretation of COL4A3 and COL4A4 mutations mean that mutation detection is not used routinely in the diagnosis of TBMN...
  22. Sachdeva A, Matuschak G. Diffuse alveolar hemorrhage following alemtuzumab. Chest. 2008;133:1476-1478 pubmed publisher
    ..The prevalence of this form of pulmonary toxicity is unclear and requires further systematic study...
  23. Ghiggeri G, Caridi G, Magrini U, Sessa A, Savoia A, Seri M, et al. Genetics, clinical and pathological features of glomerulonephritis associated with mutations of nonmuscle myosin IIA (Fechtner syndrome). Am J Kidney Dis. 2003;41:95-104 pubmed
    ..Although it recently was shown that FTNS derives from mutation of MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC-IIA), its pathophysiological characteristics remain unknown...
  24. Delanaye P, Nikkels A, Martalo O, Dechenne C, Arrese J, Rorive G, et al. [How I investigate ... Alport's syndrome by skin biopsy. When the skin speaks for the kidney]. Rev Med Liege. 2002;57:670-1 pubmed
    ..Immunohistochemistry performed on a conventional skin biopsy allows to prove the diagnosis in the affected subjects and in healthy women exhibiting the mutation on a single X chromosome...
  25. Hood J, Huxtable C, Naito I, Smith C, Sinclair R, Savige J. A novel model of autosomal dominant Alport syndrome in Dalmatian dogs. Nephrol Dial Transplant. 2002;17:2094-8 pubmed
    ..It is usually caused by mutations in the COL4A3 or COL4A4 genes which code for the alpha3 and alpha4 chains of type IV collagen. We describe here a novel spontaneous model of autosomal dominant Alport syndrome in Dalmatian dogs...
  26. King K, Flinter F, Nihalani V, Green P. Unusual deep intronic mutations in the COL4A5 gene cause X linked Alport syndrome. Hum Genet. 2002;111:548-54 pubmed
    ..All three cases would have been missed using an exon-by-exon DNA screening approach...
  27. Komatsuda A, Ohtani H, Wakui H, Tokuda N, Nakamoto Y, Sado Y, et al. A family with X-linked Alport syndrome confirmed by skin biopsy. Nephrol Dial Transplant. 2002;17:1145-7 pubmed
  28. Hudson B. The molecular basis of Goodpasture and Alport syndromes: beacons for the discovery of the collagen IV family. J Am Soc Nephrol. 2004;15:2514-27 pubmed
  29. Yachnin T, Iaina A, Schwartz D, Nakache R. The mother of an Alport's syndrome patient: a safe kidney donor?. Nephrol Dial Transplant. 2002;17:683-4 pubmed
  30. Lyons O, St John E, Morales J, Chan Y, Taylor P. Ruptured thoracoabdominal aortic aneurysm in a renal transplant patient with Alport's syndrome. Ann Vasc Surg. 2007;21:816-8 pubmed
    ..Hypotheses on an association between collagen disease in Alport's syndrome and aortic aneurysms are discussed...
  31. Heath K, Campos Barros A, Toren A, Rozenfeld Granot G, Carlsson L, Savige J, et al. Nonmuscle myosin heavy chain IIA mutations define a spectrum of autosomal dominant macrothrombocytopenias: May-Hegglin anomaly and Fechtner, Sebastian, Epstein, and Alport-like syndromes. Am J Hum Genet. 2001;69:1033-45 pubmed
    ..On the basis of our genetic analyses, the name "MYHIIA syndrome" is proposed to encompass all of these disorders...
  32. Kobayashi T, Uchiyama M. Mutant-type alpha5(IV) collagen in a mild form of Alport syndrome has residual ability to form a heterotrimer. Pediatr Nephrol. 2010;25:1169-72 pubmed publisher
    ..The residual ability of the mutant chain may have led to the unique phenotypes found in the AS family with the Cys1638Tyr mutation...
  33. Kim K, Kim M, Kim J, Choi C. Evaluation of anterior lenticonus in alport syndrome using tracey wavefront aberrometry and transmission electron microscopy. Ophthalmic Surg Lasers Imaging. 2010;41:330-6 pubmed publisher
    ..To evaluate the efficacy of Tracey wavefront aberrometry (Tracey Technologies, Houston, TX) and transmission electron microscopy for the detection of anterior lenticonus in Alport syndrome...
  34. Bower K, Edwards J, Wagner M, Ward T, Hidayat A. Novel corneal phenotype in a patient with alport syndrome. Cornea. 2009;28:599-606 pubmed publisher
    ..To report the clinical and histopathologic findings of an unusual keratopathy, which may represent a new corneal dystrophy in a patient with Alport syndrome (ATS)...
  35. Slajpah M, Meglic A, Furlan P, Glavac D. The importance of non-invasive genetic analysis in the initial diagnostics of Alport syndrome in young patients. Pediatr Nephrol. 2005;20:1260-4 pubmed
    ..Our study showed the importance of molecular genetic data for the purpose of providing quick and precise diagnoses for affected family members and their offspring, particularly small children...
  36. Pescucci C, Longo I, Mari F, Scala E, Bruttini M, Caselli R, et al. [Clinical and genetic features of the Alport 'syndromes']. G Ital Nefrol. 2005;22:466-76 pubmed
    ..We will report direct experiences of our group showing the difficulties to give an exact prognosis and a correct recurrence risk to the family...
  37. Cosgrove D, Kalluri R, Miner J, Segal Y, Borza D. Choosing a mouse model to study the molecular pathobiology of Alport glomerulonephritis. Kidney Int. 2007;71:615-8 pubmed
  38. Pelit A, Oto S, Yilmaz G, Akova Y. Spontaneous rupture of the anterior lens capsule combined with macular hole in a child with Alport's syndrome. J Pediatr Ophthalmol Strabismus. 2004;41:59-61 pubmed
  39. Rizk D, Chapman A. Cystic and inherited kidney diseases. Am J Kidney Dis. 2003;42:1305-17 pubmed
  40. Heidet L, Borza D, Jouin M, Sich M, Mattei M, Sado Y, et al. A human-mouse chimera of the alpha3alpha4alpha5(IV) collagen protomer rescues the renal phenotype in Col4a3-/- Alport mice. Am J Pathol. 2003;163:1633-44 pubmed
    ..This line of mice, humanized for the alpha3(IV) collagen chain, will also provide a valuable model for studying the pathogenesis of Goodpasture syndrome, an autoimmune disease caused by antibodies against this chain...
  41. Buzza M, Wang Y, Dagher H, Babon J, Cotton R, Powell H, et al. COL4A4 mutation in thin basement membrane disease previously described in Alport syndrome. Kidney Int. 2001;60:480-3 pubmed
    ..This study describes the first COL4A4 mutation in an individual with biopsy-proven TBMD who did not have a family member with autosomal-recessive or X-linked Alport syndrome, inherited renal failure, or deafness...
  42. Sampson N, Ryan S, Enke D, Cosgrove D, Koteliansky V, Gotwals P. Global gene expression analysis reveals a role for the alpha 1 integrin in renal pathogenesis. J Biol Chem. 2001;276:34182-8 pubmed
  43. Martin P, Heiskari N, Pajari H, Gronhagen Riska C, Kaariainen H, Koskimies O, et al. Spectrum of COL4A5 mutations in Finnish Alport syndrome patients. Hum Mutat. 2000;15:579 pubmed
    ..Three of the mutations were potential splicing mutations, two of which were studied at the mRNA level. Seven of the mutations were single base substitutions, and two were deletions. In five families, no mutations were found...
  44. Savige J, Wang Y, Rana K, Sin L, Lin T. Asymptomatic microscopic hematuria. Urology. 2002;59:631-2 pubmed
  45. Ciccarese M, Casu D, Ki Wong F, Faedda R, Arvidsson S, Tonolo G, et al. Identification of a new mutation in the alpha4(IV) collagen gene in a family with autosomal dominant Alport syndrome and hypercholesterolaemia. Nephrol Dial Transplant. 2001;16:2008-12 pubmed
    ..Rare autosomal forms of AS have been described with mutations in COL4A3 and COL4A4 at chromosome region 2q35-q37, but there have been no descriptions of dominant forms due to a mutation in COL4A4...
  46. Borza D, Bondar O, Ninomiya Y, Sado Y, Naito I, Todd P, et al. The NC1 domain of collagen IV encodes a novel network composed of the alpha 1, alpha 2, alpha 5, and alpha 6 chains in smooth muscle basement membranes. J Biol Chem. 2001;276:28532-40 pubmed
    ..The existence of the alpha1.alpha2.alpha5.alpha6 network provides a molecular explanation for the concomitant loss of alpha5 and alpha6 chains from the BMs of patients with X-linked Alport's syndrome...
  47. Fujii H, Mori Y, Kayamori K, Igari T, Ito E, Akashi T, et al. A familial case of mitochondrial disease resembling Alport syndrome. Clin Exp Nephrol. 2008;12:159-163 pubmed publisher
    ..This syndrome should be recognized by nephrologists as a differential diagnosis of Alport syndrome, diabetic nephropathy, and primary glomerular diseases...
  48. Pierides A, Voskarides K, Athanasiou Y, Ioannou K, Damianou L, Arsali M, et al. 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 kidne. Nephrol Dial Transplant. 2009;24:2721-9 pubmed publisher
    ..Heterozygous mutations in the COL4A3/ COL4A4 genes are currently thought to be responsible for familial benign microscopic haematuria and maintenance of normal long-term kidney function...
  49. Barakat A, Butrus S, Faris B, Dabbagh S. Ocular abnormalities and renal disease: a review. Metab Pediatr Syst Ophthalmol (1985). 1985;8:27-34 pubmed
    ..It also touches on these changes in some syndromes with major renal involvement...
  50. Hertz J. Alport syndrome. Molecular genetic aspects. Dan Med Bull. 2009;56:105-52 pubmed
    ..The many different animal models for AS are obvious and promising targets for functional studies, and an important resource for gene therapy studies. This makes AS a reliable candidate for future gene therapy in humans...
  51. Knebelmann B, Deschenes G, Gros F, Hors M, Grunfeld J, Zhou J, et al. Substitution of arginine for glycine 325 in the collagen alpha 5 (IV) chain associated with X-linked Alport syndrome: characterization of the mutation by direct sequencing of PCR-amplified lymphoblast cDNA fragments. Am J Hum Genet. 1992;51:135-42 pubmed
    ..This gly325-to-arg substitution presumably alters the triple-helix formation, and, in turn, modifies the ultrastructural and functional characteristics of the type IV collagen network inside the glomerular basement membrane...
  52. Tanaka M, Asada M, Higashi A, Nakamura J, Oguchi A, Tomita M, et al. Loss of the BMP antagonist USAG-1 ameliorates disease in a mouse model of the progressive hereditary kidney disease Alport syndrome. J Clin Invest. 2010;120:768-77 pubmed publisher
  53. Renieri A, Seri M, Myers J, Pihlajaniemi T, Massella L, Rizzoni G, et al. De novo mutation in the COL4A5 gene converting glycine 325 to glutamic acid in Alport syndrome. Hum Mol Genet. 1992;1:127-9 pubmed
    ..PCR amplification and DNA sequencing revealed a single G-->A nucleotide change. The mutation results in substitution of a glutamic acid for a glycine residue at position 325 in the triple helical region of the alpha 5(IV) chain...