title: Clinical characterization of a family with a mutation in the uromodulin (Tamm-Horsfall glycoprotein) gene.
abstract: BACKGROUND
  We have recently identified a mutation in the uromodulin gene in a large family affected with hyperuricemia, gout, and renal failure. The purpose of this investigation is to provide a comprehensive characterization of the clinical findings of this syndrome in family members who had a mutation in the uromodulin gene.
  
  
  METHODS
  An extended family suffering from hyperuricemia and gout was identified by a local practitioner. After consent was obtained, patients provided a directed clinical history and blood and urine specimens for chemical and genetic testing. All family members were tested for the presence of uromodulin gene mutations by direct DNA sequence analysis. The clinical and biochemical characteristics of family members carrying the affected mutation were then investigated.
  
  
  RESULTS
  Thirty-nine family members were found to have an exon 5 uromodulin gene mutation (g.1966 1922 del), and 29 unaffected family members were identified. The cardinal clinical features in individuals with the uromodulin mutation included hyperuricemia, decreased fractional excretion of uric acid, and chronic interstitial renal disease leading to end-stage renal disease (ESRD) in the fifth through seventh decade. Women did not always develop hyperuricemia or gout, but still developed progressive chronic renal failure.
  
  
  CONCLUSIONS
  Mutation of the uromodulin gene resulted in hyperuricemia, reduced fractional excretion of uric acid, and renal failure. Genetic testing will be required to definitively identify individuals suffering from this condition. We are interested in studying other families that may suffer from this condition and would appreciate any such referrals.
authors.affiliation: Section on Nephrology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. ableyer@wfubmc.edu
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bleyer
authors.forename: Arch S
authors.initials: AS
authors.lastname: Woodard
authors.forename: Zak
authors.initials: Z
authors.lastname: Shihabi
authors.forename: Jaspreet
authors.initials: J
authors.lastname: Sandhu
authors.forename: Honping
authors.initials: H
authors.lastname: Zhu
authors.forename: Scott G
authors.initials: SG
authors.lastname: Satko
authors.forename: Nelson
authors.initials: N
authors.lastname: Weller
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Deterding
authors.forename: Debra
authors.initials: D
authors.lastname: McBride
authors.forename: Michael C
authors.initials: MC
authors.lastname: Gorry
authors.forename: Linda
authors.initials: L
authors.lastname: Xu
authors.forename: Deann
authors.initials: D
authors.lastname: Ganier
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Hart
mesh_terms: D000293:Adolescent; D000483:Alleles; D020029:Base Pairing / Q000235:genetics; D002908:Chronic Disease; D003404:Creatinine / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D005799:Genes, Dominant; D006073:Gout / Q000235:genetics*; D006801:Humans; D033461:Hyperuricemia / Q000235:genetics* / Q000473:pathology / Q000652:urine; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000209:etiology; D008297:Male; D009088:Mucoproteins / Q000235:genetics*; D009154:Mutation; D009994:Osmolar Concentration; D014527:Uric Acid / Q000652:urine; D014556:Urine / Q000737:chemistry; D058949:Uromodulin
chemical_list: D009088:Mucoproteins; C548612:UMOD protein, human; D058949:Uromodulin; D014527:Uric Acid; D003404:Creatinine