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

Abstract

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.

• Authors: Coralie Bingham, 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
• Journal: Kidney international (Kidney Int) Vol. 63 Issue 5 Pg. 1645-51 (May 2003) ISSN: 0085-2538 [Print] United States
• PMID: 12675839 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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)