[HTML][HTML] Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1β gene mutation
C Bingham, S Ellard, WG Van't Hoff, HA Simmonds… - Kidney international, 2003 - Elsevier
C Bingham, S Ellard, WG Van't Hoff, HA Simmonds, AM Marinaki, MK Badman, PH Winocour…
Kidney international, 2003•ElsevierAtypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear
factor-1β gene mutation. 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 …
factor-1β gene mutation. 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 …
Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1β gene mutation.
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+1G>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 μmol/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.
Elsevier