title: Novel uromodulin mutation in familial juvenile hyperuricemic nephropathy.
abstract: BACKGROUND
  Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder characterized by early onset of hyperuricemia, decreased fractional renal urate excretion and progressive interstitial nephropathy. Mutations in the uromodulin (UMOD) gene encoding uromodulin/Tamm-Horsfall, a glycosylphosphatidylinositol (GPI)-anchored protein, cause this disease.
  
  
  METHODS
  One Chinese family with 13 FJHN-affected individuals is described. Clinical data, blood and urine samples of 7 affected members (all alive patients in this family) and 15 unaffected members were collected. Mutation analysis of the UMOD gene was performed by polymerase chain reaction and direct sequencing. Urinary uromodulin from affected or unaffected members of this family and healthy controls was examined by enzyme-linked immunosorbent assay kit. Expression of uromodulin in renal tissue was shown with immunofluorescence.
  
  
  RESULTS
  A novel mutation (p.T605G) within the uromodulin GPI anchor signal segment was identified in the affected individuals of this FJHN family. There was a markedly increased expression of uromodulin in renal tissue and significantly decreased urinary excretion of uromodulin in affected patients with an estimated glomerular filtration rate <60 ml/min/1.73 m(2).
  
  
  CONCLUSIONS
  The present study reported a novel mutation in exon 9 of UMOD in the Chinese Han population, within the GPI anchor signal segment of uromodulin. Since the GPI anchor is linked with the release or secretion of proteins, our finding may provide further evidence for the underlying mechanism of decreased urinary excretion of uromodulin in FJHN.
authors: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Key Laboratory of Nephrology, Ministry of Health, Guangzhou, PR China.
authors: Xin
authors: X
authors: Wei
authors: Ricong
authors: R
authors: Xu
authors: Zhenhua
authors: Z
authors: Yang
authors: Zhijian
authors: Z
authors: Li
authors: Yunhua
authors: Y
authors: Liao
authors: Richard J
authors: RJ
authors: Johnson
authors: Xueqing
authors: X
authors: Yu
authors: Wei
authors: W
authors: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D006073:Gout / Q000235:genetics* / Q000473:pathology; D006801:Humans; D033461:Hyperuricemia / Q000235:genetics* / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D058949:Uromodulin / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: C548612:UMOD protein, human; D058949:Uromodulin