Clinical spectrum associated with hepatocyte nuclear factor-1beta mutations.

Area of Science:

• Genetics
• Endocrinology
• Nephrology

Background:

• Maturity-onset diabetes of the young type 5 (MODY5) is an inherited condition linked to hepatocyte nuclear factor-1beta (HNF-1beta) gene mutations, often resulting in truncated proteins.
• HNF-1beta mutations are associated with diverse phenotypes, including diabetes mellitus, nephropathy, and urogenital malformations.

Purpose of the Study:

• To investigate the clinical and genetic characteristics of 13 patients with 8 novel HNF-1beta mutations.
• To explore the phenotypic spectrum associated with HNF-1beta mutations in MODY5.

Main Methods:

• A multicenter descriptive study involving patients from diabetes, internal medicine, and nephrology departments.
• Clinical data collection included diabetes characteristics, renal function and structure, genital and pancreatic abnormalities, and liver function tests.
• Genetic analysis focused on identifying and characterizing HNF-1beta mutations in probands and their offspring.

Main Results:

• Eight novel HNF-1beta mutations were identified, primarily in the DNA-binding domain, with 5 missense changes.
• Diabetes was present in 10 of 13 carriers, with variable clinical presentation.
• Renal involvement, pancreatic atrophy, exocrine insufficiency, and genital abnormalities were frequently observed, alongside abnormal liver enzyme levels.

Conclusions:

• MODY5 presents a broad clinical spectrum, underscoring the importance of HNF-1beta mutation analysis.
• Genetic testing for HNF-1beta mutations is advisable in nonobese patients with diabetes and progressive nondiabetic nephropathy, especially with pancreatic or genital anomalies, irrespective of family history.