Mutations in the hepatocyte nuclear factor (HNF)-1β gene (TCF2) are responsible for a syndrome characterized by maturity-onset diabetes of the young, a nondiabetic renal disease, genital malformations, and liver dysfunction.

The HNF-1β gene was screened for mutations in four members of an Italian family with early-onset, nonketotic diabetes or a familiar, nondiabetic renal disease and nonprogressive liver disorder.

The genetic analysis revealed an already described nonsense mutation in codon 177 of HNF-1β gene (R177X) in the four related subjects. Clinical features included diabetes in three of four patients, monolateral renal hypoplasia with cysts in the controlateral kidney in two patients, and bilaterally small hyperechoic kidneys without cysts in the other two patients. Renal function impairment was severe in one patient, requiring dialysis treatment, and mild in three. Three patients had nonprogressive liver dysfunction, with long-lasting enzyme alterations but no liver insufficiency or jaundice.

HNF-1β gene mutations are associated with a wide variability in severity and pattern of clinical symptoms within the same kindred regarding diabetes and renal impairment. Moderate liver dysfunction may be a so far overlooked component of the syndrome.