title: Familial nephropathy associated with hyperuricemia in Spain: our experience with 3 families harbouring a UMOD mutation.
abstract: Since 1993 we have studied 5 Spanish families with familial nephropathy associated with hyperuricemia (FJHN). Among these families, 24 patients have been identified. All patients had some combination of hyperuricemia, gout, renal insufficiency, arterial hypertension, and reduced kidney size. The clinical presentation in the different families and in the members of the same family was heterogeneous. Allopurinol treatment did not appear to influence renal disease. From a clinical perspective, this syndrome is a distinctive interstitial nephropathy, inherited as an autosomal dominant trait, that progresses to renal failure and is not halted nor prevented by allopurinol therapy. In 2003, genetic linkage analysis in 3 of the 5 families showed linkage of FJHN to 16p 11.2. One family was not analyzed and one family did not show linkage to this region confirming the genetic heterogeneity of this syndrome. A mutation in UMOD gene was found in these 3 families as the cause of the FJHN. The mutations cluster in exon 4 and exon 5 and were point mutation that results in an amino acid change in the uromodulin or Tamm Horsfall protein. This fact allowed in 2004, the presymptomatic genetic diagnosis of an 8-years-old boy belonging to one of these 3 Spanish families. We conclude that in families with a history of renal failure and/or gout in which FJHN is suspected, UMOD mutation screening may enable a definite diagnosis. When a mutation is found, family members can be tested for a UMOD mutation and pre-symptomatic diagnosis may allow counseling to prevent or halt the progression to renal insufficiency.
authors.affiliation: Division of Internal Medicine, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: J G
authors.initials: JG
authors.lastname: Puig
authors.forename: C
authors.initials: C
authors.lastname: Prior
authors.forename: J
authors.initials: J
authors.lastname: Martínez-Ara
authors.forename: R J
authors.initials: RJ
authors.lastname: Torres
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005091:Exons; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D033461:Hyperuricemia / Q000175:diagnosis* / Q000235:genetics*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009088:Mucoproteins / Q000235:genetics*; D009154:Mutation; D051437:Renal Insufficiency / Q000175:diagnosis / Q000235:genetics*; D014527:Uric Acid / Q000378:metabolism; D058949:Uromodulin
chemical_list: D009088:Mucoproteins; C548612:UMOD protein, human; D058949:Uromodulin; D014527:Uric Acid