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Kidney Int. 2003 May;63(5):1645-51.

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

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Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, United Kingdom.



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.


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.


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).


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.

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