HNF1B-associated clinical phenotypes: the kidney and beyond

Area of Science:

• Genetics and Molecular Biology
• Nephrology
• Developmental Biology

Background:

• Mutations in the hepatocyte nuclear factor 1β (HNF1B) gene are the most frequent genetic cause of renal malformations.
• Initially identified in monogenic diabetes of youth type 5 (MODY5), HNF1B's role in renal disease was later recognized.

Purpose of the Study:

• To review the spectrum of phenotypes associated with HNF1B mutations.
• To discuss the clinical management implications of HNF1B-related disorders.

Main Methods:

• Literature review of HNF1B-associated phenotypes.
• Analysis of clinical observations and genetic data.

Main Results:

• HNF1B mutations lead to a wide range of phenotypes including renal, genital, and neurological abnormalities, as well as metabolic disorders like gout and hypomagnesaemia.
• A common 17q12 chromosomal microdeletion, encompassing HNF1B, accounts for approximately 50% of mutations and is associated with specific neurological phenotypes.
• Some phenotypes may be linked to other genes within the microdeletion rather than HNF1B itself.

Conclusions:

• HNF1B is a critical gene for kidney development, and its mutations cause a complex syndrome with diverse clinical manifestations.
• Understanding the full spectrum of HNF1B-associated phenotypes, including those linked to the 17q12 microdeletion, is crucial for accurate diagnosis and management.