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

Coralie Bingham (Lead / Corresponding author), Sian Ellard, William G. Van't Hoff, H. Anne Simmonds, Anthony M. Marinaki, Michael K. Badman, Peter H. Winocour, Amanda Stride, Christopher R. Lockwood, Anthony J. Nicholls, Katharine R. Owen, Ghislaine Spyer, Ewan R. Pearson, Andrew T. Hattersley

Research output: Contribution to journalArticlepeer-review

139 Citations (Scopus)


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)-1β 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-1β gene in some FJHN kindreds we sequenced the HNF-1β 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-1β mutations with populations of controls, type 2 diabetic subjects, and subjects with mild chronic renal failure without HNF-1β mutations.

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

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

Original languageEnglish
Pages (from-to)1645-1651
Number of pages7
JournalKidney International
Issue number5
Publication statusPublished - May 2003


  • Familial renal disease
  • HNF-1β mutation
  • Hyperuricemia
  • Juvenile gout
  • Transcription factors

ASJC Scopus subject areas

  • Nephrology


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