HNF1B MODY & RCAD
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.
HNF1B Related Diabetes & Renal Disease
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
- Single kidney
- Early onset non-insulin dependent diabetes
- Genital tract malformations
- Hyperuricaemia and early onset gout
- Hypomagnesaemia
- Abnormal liver function tests
- Autism spectrum disorder
- Pancreatic exocrine deficiency
- Neurodevelopmental disorders including autism spectrum disorder
Genetic Testing
Genetic testing for pathogenic variants in the HNF1B gene is available from the Molecular Genetics Laboratory at the Royal Devon University Healthcare NHS Foundation Trust.
Information for Patients & Clinicians
The following external links provide clearly written information and advice on HNF1B related disease to patients and their clinicians.
Information for patients:
HNF1B patient information days have been held in 2012, 2016, 2017, 2018, 2021 and 2024.
Presentations from these events are available to download here under ‘Recent Activities’
Referral to Exeter specialist MDT clinic
Specialist multidisciplinary clinics for adults and children with HNF1B-associated disease
Purpose of the service
Our new, national clinical service will offer patients with HNF1B related disease the opportunity to see a series of specialist healthcare professionals in one visit. These specialists will provide clinical assessments and advice for each of the different aspects of the patient’s condition. For example, people with HNF1B-associated disease can have abnormalities of the kidney and urinary tract, diabetes and several other features. The findings from each of the specialists will be reported back to the referring clinician in a single document along with any ongoing recommendations for the patient’s clinical care.
The clinics
Clinics will be held every four months in the NIHR Exeter Clinical Research Facility, with separate clinics for adults and children.
Investigations and tests
All individuals who come to the clinic should have blood tests undertaken locally prior to their attendance so that the results are available on the day of their visit to Exeter. The specific blood tests required will be outlined in the clinic invitation letter. Some individuals may be asked to complete questionnaires about development and mental health prior to their attendance.
A series of further tests may be done during the clinic visit. These could include;
- Measurement of height and weight
- Blood pressure
- Urinalysis
- Urinary C-peptide creatinine ratio (UCPCR)
- Faecal elastase
- Screening for neurodevelopmental / psychiatric disorders or neuropsychological impairments
Professionals seen in clinic
During the clinic, each individual and (if present) their family / carer will meet with a range of healthcare professionals with specialist knowledge of this condition in a series of separate consultations. The specific professionals involved will vary depending on the age of the individual and how the condition affects them, but may include;
- Diabetologist
- Diabetes nurse specialist
- Paediatric nephrologist
- Adult nephrologist
- Geneticist
- Dietician
- Research nurse or research practitioner
Each clinic attendance will take up to 3 hours.
Research
Individuals attending the clinic will also be offered the opportunity to take part in research studies that may be of interest to them. There will be no obligation to take part and decisions will not influence their clinical care.
How to refer to the service
Referrals are accepted from GPs, hospital Consultants, or individual patients (self-funded). Please send referral letters to:
Georgia Turvey
Diabetes, Endocrine & Obesity Services
The MacLeod Diabetes & Endocrine Centre (MDEC)
Royal Devon University Healthcare NHS Foundation Trust (RDE Hospital, Wonford), Exeter EX2 5DW
or alternatively e-mail referral letters or enquiries about the service to:
HNF1B Patient Groups
The National Rare Disease Registry (RaDaR)
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.
Contacts
HNF1B & Renal Disease
Dr Coralie Bingham
Address: Exeter Kidney Unit, Royal Devon University Healthcare NHS Foundation Trust, Barrack Road, Exeter, EX2 5DW
Phone: +44 1392 40 6366
Email: c.bingham@exeter.ac.uk or use coralie.bingham@nhs.net for patient confidential information
HNF1B & Diabetes
Professor Andrew Hattersley
Address: RILD Building Level 3, Royal Devon University Healthcare NHS Foundation Trust, Barrack Road, Exeter, EX2 5DW
Email: a.t.hattersley@exeter.ac.uk
HNF1B Genetic Testing
Kevin Colclough
Address: Molecular Genetics Laboratory, RILD Building Level 3, Royal Devon University Healthcare NHS Foundation Trust, Barrack Road, Exeter, EX2 5DW
Phone: +44 1392 40 8324
Email: kevin.colclough@nhs.net
References
Dubois-Laforgue D, Cornu E, Saint-Martin C, Coste J, Bellanne-Chantelot C, Timsit J, Monogenic Diabetes Study Group of the Societe Francophone du D: Diabetes, Associated Clinical Spectrum, Long-term Prognosis and Genotype/Phenotype Correlations in 201 Adult Patients With Hepatocyte Nuclear Factor 1 B (HNF1B) Molecular Defects. Diabetes Care 2017, 40(11):1436-1443
Clissold RL, Shaw-Smith C, Turnpenny P, Bunce B, Bockenhauer D, Kerecuk L, Waller S, Bowman P, Ford T, Ellard S et al: Chromosome 17q12 microdeletions but not intragenic HNF1B mutations link developmental kidney disease and psychiatric disorder. Kidney Int 2016, 90(1):203-211.
Clissold RL, Hamilton AJ, Hattersley AT, Ellard S, Bingham C: HNF1B-associated renal and extra-renal disease-an expanding clinical spectrum. Nat Rev Nephrol 2015, 11(2):102-112
Clissold R, Shields B, Ellard S, Hattersley A, Bingham C: Assessment of the HNF1B Score as a Tool to Select Patients for HNF1B Genetic Testing. Nephron 2015, 130(2):134-140
Laffargue F, Bourthoumieu S, Llanas B, Baudouin V, Lahoche A, Morin D, Bessenay L, De Parscau L, Cloarec S, Delrue MA et al: Towards a new point of view on the phenotype of patients with a 17q12 microdeletion syndrome. Arch Dis Child 2015, 100(3):259-264.
Raaijmakers A, Corveleyn A, Devriendt K, van Tienoven TP, Allegaert K, Van Dyck M, van den Heuvel L, Kuypers D, Claes K, Mekahli D et al: Criteria for HNF1B analysis in patients with congenital abnormalities of kidney and urinary tract. Nephrol Dial Transplant 2015, 30(5):835-842.
Faguer S, Chassaing N, Bandin F, Prouheze C, Garnier A, Casemayou A, Huart A, Schanstra JP, Calvas P, Decramer S et al: The HNF1B score is a simple tool to select patients for HNF1B gene analysis. Kidney Int 2014, 86(5):1007-15
Faguer S, Decramer S, Chassaing N, Bellanne-Chantelot C, Calvas P, Beaufils S, Bessenay L, Lengele JP, Dahan K, Ronco P et al: Diagnosis, management, and prognosis of HNF1B nephropathy in adulthood. Kidney Int 2011, 80(7):768-776.
Loirat C, Bellanne-Chantelot C, Husson I, Deschenes G, Guigonis V, Chabane N: Autism in three patients with cystic or hyperechogenic kidneys and chromosome 17q12 deletion. Nephrol Dial Transplant 2010, 25(10):3430-3433.
Moreno-De-Luca D, Mulle JG, Kaminsky EB, Sanders SJ, Myers SM, Adam MP, Pakula AT, Eisenhauer NJ, Uhas K, Weik L et al: Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia. Am J Hum Genet 2010, 87(5):618-630.
Oram RA, Edghill EL, Blackman J, Taylor MJ, Kay T, Flanagan SE, Ismail-Pratt I, Creighton SM, Ellard S, Hattersley AT et al: Mutations in the hepatocyte nuclear factor-1beta (HNF1B) gene are common with combined uterine and renal malformations but are not found with isolated uterine malformations. Am J Obstet Gynecol 2010, 203(4):364 e361-365.
Heidet L, Decramer S, Pawtowski A, Moriniere V, Bandin F, Knebelmann B, Lebre AS, Faguer S, Guigonis V, Antignac C et al: Spectrum of HNF1B mutations in a large cohort of patients who harbor renal diseases. Clin J Am Soc Nephrol 2010, 5(6):1079-1090.
Adalat S, Woolf AS, Johnstone KA, Wirsing A, Harries LW, Long DA, Hennekam RC, Ledermann SE, Rees L, van’t Hoff W et al: HNF1B mutations associate with hypomagnesemia and renal magnesium wasting. J Am Soc Nephrol 2009, 20(5):1123-1131.
Haldorsen IS, Vesterhus M, Raeder H, Jensen DK, Sovik O, Molven A, Njolstad PR: Lack of pancreatic body and tail in HNF1B mutation carriers. Diabet Med 2008, 25(7):782-787.
Decramer S, Parant O, Beaufils S, Clauin S, Guillou C, Kessler S, Aziza J, Bandin F, Schanstra JP, Bellanne-Chantelot C: Anomalies of the TCF2 gene are the main cause of fetal bilateral hyperechogenic kidneys. J Am Soc Nephrol 2007, 18(3):923-933.
Bellanne-Chantelot C, Clauin S, Chauveau D, Collin P, Daumont M, Douillard C, Dubois-Laforgue D, Dusselier L, Gautier JF, Jadoul M et al: Large genomic rearrangements in the hepatocyte nuclear factor-1beta (TCF2) gene are the most frequent cause of maturity-onset diabetes of the young type 5. Diabetes 2005, 54(11):3126-3132.
Bingham C, Hattersley AT: Renal cysts and diabetes syndrome resulting from mutations in hepatocyte nuclear factor-1beta. Nephrol Dial Transplant 2004, 19(11):2703-2708.
Bingham C, Ellard S, van’t Hoff WG, Simmonds HA, Marinaki AM, Badman MK, Winocour PH, Stride A, Lockwood CR, Nicholls AJ et al: Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1beta gene mutation. Kidney Int 2003, 63(5):1645-1651.
Bingham C, Bulman MP, Ellard S, Allen LI, Lipkin GW, Hoff WG, Woolf AS, Rizzoni G, Novelli G, Nicholls AJ et al: Mutations in the hepatocyte nuclear factor-1beta gene are associated with familial hypoplastic glomerulocystic kidney disease. Am J Hum Genet 2001, 68(1):219-224.
Bingham C, Ellard S, Allen L, Bulman M, Shepherd M, Frayling T, Berry PJ, Clark PM, Lindner T, Bell GI et al: Abnormal nephron development associated with a frameshift mutation in the transcription factor hepatocyte nuclear factor-1 beta. Kidney Int 2000, 57(3):898-907.
HNF1B Information for Clinicians 02.06.2017 HNF1B Information for Patients 02.06.2017