title: Autosomal dominant tubulointerstitial kidney disease caused by uromodulin mutations: seek and you will find.
abstract: BACKGROUND
  Uromodulin (UMOD)-associated kidney disease belongs to the group of autosomal dominant interstitial kidney diseases and is caused by mutations in the UMOD gene. Affected patients present with hyperuricemia, gout, and progressive renal failure. The disease is thought to be very rare but is probably underdiagnosed.
  
  
  METHODS
  Two index patients from two families with tubulointerstitial nephropathy and hyperuricemia were examined, including blood and urine chemistry, ultrasound, and mutation analysis of the UMOD gene. In addition, other available family members were studied.
  
  
  RESULTS
  In a 46-year-old female patient with a fractional excretion of uric acid of 3 %, analysis of the UMOD gene revealed a p.W202S missense mutation. The same mutation was found in her 72-year-old father, who suffers from gout and end-stage renal disease. The second index patient was a 47-year-old female with chronic kidney disease and gout for more than 10 years. Her fractional uric acid excretion was 3.5 %. Genetic analysis identified a novel p.H250Q UMOD mutation that was also present in her 12-year-old son, who had normal renal function and uric acid levels.
  
  
  CONCLUSIONS
  In patients suffering from chronic tubulointerstitial nephropathy, hyperuricemia, and a low fractional excretion of uric acid mutation, analysis of the UMOD gene should be performed to diagnose UMOD-associated kidney disease.
authors.affiliation: Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, Carinagasse 47, 6800, Feldkirch, Austria.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Raffler
authors.affiliation: Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, Carinagasse 47, 6800, Feldkirch, Austria.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Zitt
authors.affiliation: Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, Carinagasse 47, 6800, Feldkirch, Austria.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Sprenger-Mähr
authors.affiliation: Laboratory for Molecular Diagnostics, Center for Nephrology and Metabolic Disorders, Weißwasser, Germany.
authors.forename: Mato
authors.initials: M
authors.lastname: Nagel
authors.affiliation: Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, Carinagasse 47, 6800, Feldkirch, Austria. Karl.lhotta@lkhf.at.
authors.forename: Karl
authors.initials: K
authors.lastname: Lhotta
mesh_terms: D003937:Diagnosis, Differential; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016891:Polycystic Kidney, Autosomal Dominant / Q000175:diagnosis* / Q000235:genetics*; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis* / Q000235:genetics*; D058949:Uromodulin / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C548612:UMOD protein, human; D058949:Uromodulin
keywords: Chronic kidney disease; Fractional uric acid excretion; Gout; Tubulointerstitial kidney disease; Uromodulin
references.citation: J Biol Chem. 2011 Aug 26;286(34):30200-10
references.pmid: 21737451
references.citation: Nephron. 1998;79(3):340-4
references.pmid: 9678437
references.citation: Adv Exp Med Biol. 1994;370:91-3
references.pmid: 7661034
references.citation: Clin J Am Soc Nephrol. 2011 Oct;6(10):2429-38
references.pmid: 21868615
references.citation: Hum Mol Genet. 2003 Dec 15;12(24):3369-84
references.pmid: 14570709
references.citation: Nephrol Dial Transplant. 2010 Jun;25(6):1896-903
references.pmid: 20075439
references.citation: Am J Kidney Dis. 2003 Oct;42(4):658-76
references.pmid: 14520616
references.citation: Am J Hum Genet. 2009 Aug;85(2):204-13
references.pmid: 19664745
references.citation: Nat Genet. 2013 Mar;45(3):299-303
references.pmid: 23396133
references.citation: Clin Transplant. 2014 Sep;28(9):995-1003
references.pmid: 24961278
references.citation: Kidney Int. 2015 Oct;88(4):676-83
references.pmid: 25738250
references.citation: Kidney Int. 2004 May;65(5):1589-97
references.pmid: 15086896
references.citation: J Am Soc Nephrol. 2016 Feb;27(2):345-53
references.pmid: 26319241
references.citation: J Med Genet. 2002 Dec;39(12):882-92
references.pmid: 12471200
references.citation: J Am Soc Nephrol. 2003 Nov;14(11):2883-93
references.pmid: 14569098
references.citation: Nephron Extra. 2012 Jan;2(1):147-58
references.pmid: 22740033
references.citation: Hum Mol Genet. 1999 Oct;8(11):2001-8
references.pmid: 10484768