The HNF1B gene provides instructions for making a protein called a transcription factor that binds to specific regions of DNA and regulates the activity of other genes. The HNF1B protein is found in many organs and tissues, including the lungs, liver, intestines, pancreas, kidneys, reproductive system, and urinary tract, and plays a role in the development of many of these parts of the body.
Pathogenic variants and deletions of the HNF1B gene result in a number of different clinical features. The most commonly occurring conditions are renal abnormalities (renal cysts or renal structural abnormalities) and a form of diabetes known as Maturity-Onset Diabetes of the Young (MODY). The combination of renal cysts and diabetes due to HNF1B is known as the Renal Cysts and Diabetes (RCAD) syndrome.
Clinical Features that would indicate genetic testing of the HNF1B gene is required:
Unexplained renal cystic disease
Renal cysts may be detected in utero
Early onset non-insulin dependent diabetes
Genital tract malformations
Hyperuricaemia and early onset gout
Abnormal liver function tests
Autism spectrum disorder
Pancreatic exocrine deficiency
Neurodevelopmental disorders including autism spectrum disorder
Genetic testing for pathogenic variants in the HNF1B gene is available from the Molecular Genetics Laboratory at the Royal Devon & Exeter Hospital.
Clinicians with patients affected with HNF1B related renal disease are encouraged to register them on the National Registry of Rare Kidney Diseases (RaDaR). RaDaR facilitates translational and epidemiological research into rare diseases through a comprehensive clinical database. RaDaR is managed by the UK Renal Registry on behalf of the Renal Association. Recruitment to RaDaR is open to all UK hospitals; see http://rarerenal.org/radar-registry/ for details.
HNF1B & Renal Disease
Dr Coralie Bingham
Address: Exeter Kidney Unit, Royal Devon and Exeter NHS Foundation Trust, Barrack Road, Exeter, EX2 5DW
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