Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1beta gene mutation

Kidney Int. 2003 May;63(5):1645-51. doi: 10.1046/j.1523-1755.2003.00903.x.


Background: Familial juvenile hyperuricemic nephropathy (FJHN) is a dominantly inherited condition characterized by young-onset hyperuricemia, gout, and renal disease. The etiologic genes are unknown, although a locus on chromosome 16 has been identified in some kindreds. Mutations in the gene encoding hepatocyte nuclear factor (HNF)-1beta have been associated with dominant inheritance of a variety of disorders of renal development, particularly renal cystic disease and early onset diabetes; hyperuricemia has been reported in some kindreds.

Methods: To assess a possible role for the HNF-1beta gene in some FJHN kindreds we sequenced the HNF-1beta gene in subjects from three unrelated FJHN families with atypical features of renal cysts or abnormalities of renal development. We also compared serum urate levels in subjects with HNF-1beta mutations with populations of controls, type 2 diabetic subjects, and subjects with mild chronic renal failure without HNF-1beta mutations.

Results: A splice-site mutation in intron 2, designated IVS2+1G>T, showed complete co-segregation with FJHN in one family with diabetes. Serum urate levels were significantly higher in the HNF-1beta subjects compared with the normal control subjects (384 micromol/L vs. 264 micromol/L, P = 0.002) and the type 2 diabetic subjects (397 micromol/L vs. 271 micromol/L, P = 0.01). Comparison of serum urate levels in the HNF-1beta subjects with gender-matched subjects with renal impairment of other causes did not reach significance (402 micromol/L vs. 352 micromol/L, P = 0.2).

Conclusion: Hyperuricemia and young-onset gout are consistent features of the phenotype associated with HNF-1beta mutations, but the mechanism is uncertain. Families with HNF-1beta mutations may fit diagnostic criteria for FJHN. Identification of HNF-1beta patients by recognizing the features of diabetes and disorders of renal development is important in resolving the genetic heterogeneity in FJHN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child
  • DNA-Binding Proteins / genetics*
  • Family Health
  • Female
  • Gout / genetics*
  • Hepatocyte Nuclear Factor 1-beta
  • Humans
  • Hyperuricemia / genetics*
  • Kidney Diseases / genetics*
  • Male
  • Pedigree
  • Phenotype
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • HNF1B protein, human
  • Transcription Factors
  • Hepatocyte Nuclear Factor 1-beta