Genotype and Phenotype Analyses in Pediatric Patients with HNF1B Mutations

Area of Science:

• Genetics
• Pediatric Nephrology
• Molecular Biology

Background:

• HNF1B mutations are a leading cause of congenital anomalies of the kidney and urinary tract (CAKUT).
• These mutations present diverse renal and extrarenal phenotypes, complicating diagnosis.
• Understanding genotype-phenotype correlations is crucial for managing affected pediatric patients.

Purpose of the Study:

• To analyze genotype-phenotype correlations in pediatric patients with HNF1B mutations.
• To investigate the spectrum of renal and extrarenal manifestations associated with HNF1B mutations.
• To identify factors influencing diagnostic rates and clinical presentation.

Main Methods:

• Retrospective analysis of 14 pediatric patients with HNF1B mutations.
• Genetic studies including total gene deletion analysis.
• Clinical data collection on renal function, extrarenal phenotypes, and HNF1B scores.

Main Results:

• All 14 patients had bilateral renal abnormalities, mainly multiple renal cysts.
• Twelve patients showed progressive renal decline, with six reaching kidney failure (annual eGFR reduction of -2.1 mL/min/1.73 m²).
• Diabetes (36%) and neurological deficits (21%) were observed; pancreatic abnormalities were more frequent with missense mutations. No significant genotype-phenotype correlation was found for renal outcomes or extrarenal manifestations.

Conclusions:

• HNF1B mutations lead to significant renal morbidity, including progressive kidney failure.
• The extreme phenotypic variability and incomplete penetrance of HNF1B mutations pose diagnostic challenges.
• Considering patient age is vital for increasing diagnostic rates, as some phenotypes manifest over time.