Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders
This transcription factor plays a key role in pancreatic beta cell function, so mutations in TCF1 cause autosomal dominant maturity-onset diabetes of the young type 3 (MODY3) and hyperinsulinemic hypoglycemia. Some mutations are also associated with renal dysplasia and hypopituitarism.
MODY 3 Diabetes is one of the most common types of MODY. About 10% of MODY in Germany is caused by mutations of this transcription factor. These mutations could be found worldwide.
The gene also known as hepatic nuclear factor is now called TCF1. Locus is on chromosome 12 (12q24.2). Size is about 24kb. Is consists of 12 Exons. 10 of them are translated.
Mutations in this gene are responsible for autosomal dominant MODY 3 diabetes. Biochemically the picture is similar to type 2 diabetes but manifestation is early in life and there is no metabolic syndrome. In contrast to MODY 2 diabetes this type of MODY is progressive. Over the time Patients require insulin therapy and develop diabetic injuries The diabetes becomes apparent in situations of metabolic stress i.e. in pregnancy or during medication with glucocorticoids.
The protein product of this gene is a transcription factor involved in the regulation of many different genes. The exact mechanism leading to diabetes is not known.
Patients with family history and laboratory data suspect for MODY diabetes. Screening of family member in a known MODY family.
The detection of a mutation in this gene is a prerequisite for the diagnosis.
| Clinic | Method | Carrier testing |
| Turnaround | 5 days | |
| Specimen type | genomic DNA |
| Clinic | Method | Massive parallel sequencing |
| Turnaround | 25 days | |
| Specimen type | genomic DNA |
| Clinic | Method | Genomic sequencing of the entire coding region |
| Turnaround | 20 days | |
| Specimen type | genomic DNA |
| Clinic | Method | Multiplex Ligation-Dependent Probe Amplification |
| Turnaround | 20 days | |
| Specimen type | genomic DNA |
| 1. |
Triggs-Raine BL et al. (2002) HNF-1alpha G319S, a transactivation-deficient mutant, is associated with altered dynamics of diabetes onset in an Oji-Cree community. 
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| 2. |
Chèvre JC et al. (1998) Mutation screening in 18 Caucasian families suggest the existence of other MODY genes.
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| 3. |
Frayling TM et al. (1997) A rapid screening method for hepatocyte nuclear factor 1 alpha frameshift mutations; prevalence in maturity-onset diabetes of the young and late-onset non-insulin dependent diabetes.
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| 4. |
Gragnoli C et al. (1997) Maturity-onset diabetes of the young due to a mutation in the hepatocyte nuclear factor-4 alpha binding site in the promoter of the hepatocyte nuclear factor-1 alpha gene.
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| 5. |
Yamada S et al. (1997) Identification of mutations in the hepatocyte nuclear factor (HNF)-1 alpha gene in Japanese subjects with IDDM.
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| 6. |
Vaxillaire M et al. (1997) Identification of nine novel mutations in the hepatocyte nuclear factor 1 alpha gene associated with maturity-onset diabetes of the young (MODY3).
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| 7. |
Hansen T et al. (1997) Novel MODY3 mutations in the hepatocyte nuclear factor-1alpha gene: evidence for a hyperexcitability of pancreatic beta-cells to intravenous secretagogues in a glucose-tolerant carrier of a P447L mutation.
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| 8. |
Kaisaki PJ et al. (1997) Mutations in the hepatocyte nuclear factor-1alpha gene in MODY and early-onset NIDDM: evidence for a mutational hotspot in exon 4.
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| 9. |
Yamagata K et al. (1996) Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3)
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| 10. |
Byrne MM et al. (1996) Altered insulin secretory responses to glucose in diabetic and nondiabetic subjects with mutations in the diabetes susceptibility gene MODY3 on chromosome 12.
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| 11. |
Mendel DB et al. (1991) HNF-1 alpha and HNF-1 beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro.
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| 12. |
Rey-Campos J et al. (1991) vHNF1 is a homeoprotein that activates transcription and forms heterodimers with HNF1.
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| 13. |
De Simone V et al. (1991) LFB3, a heterodimer-forming homeoprotein of the LFB1 family, is expressed in specialized epithelia.
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| 14. |
None (2003) Regulation of pancreatic beta-cell function by the HNF transcription network: lessons from maturity-onset diabetes of the young (MODY).
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| 15. |
Babaya N et al. (2003) Association of I27L polymorphism of hepatocyte nuclear factor-1 alpha gene with high-density lipoprotein cholesterol level.
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| 16. |
Bjørkhaug L et al. (2003) Hepatocyte nuclear factor-1 alpha gene mutations and diabetes in Norway.
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| 17. |
Xu JY et al. (2002) Mutations in the hepatocyte nuclear factor-1alpha gene in Chinese MODY families: prevalence and functional analysis.
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| 18. |
Fajans SS et al. (2001) Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young.
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| 19. |
Stanescu DE et al. (2012) Novel Presentations of Congenital Hyperinsulinism due to Mutations in the MODY genes: HNF1A and HNF4A.
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| 20. |
Rebouissou S et al. (2005) Germline hepatocyte nuclear factor 1alpha and 1beta mutations in renal cell carcinomas.
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| 21. |
Miedzybrodzka Z et al. (1999) Non-penetrance in a MODY 3 family with a mutation in the hepatic nuclear factor 1alpha gene: implications for predictive testing.
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| 22. |
Godart F et al. (2000) Identification of seven novel nucleotide variants in the hepatocyte nuclear factor-1alpha (TCF1) promoter region in MODY patients.
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| 23. |
Hegele RA et al. (2000) Peroxisome proliferator-activated receptor-gamma2 P12A and type 2 diabetes in Canadian Oji-Cree.
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| 24. |
Chiu KC et al. (2000) The I27L amino acid polymorphism of hepatic nuclear factor-1alpha is associated with insulin resistance.
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| 25. |
None (2000) Hepatocyte nuclear factor 1 alpha (HNF-1 alpha) mutations in maturity-onset diabetes of the young.
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| 26. |
Bjørkhaug L et al. (2000) MODY associated with two novel hepatocyte nuclear factor-1alpha loss-of-function mutations (P112L and Q466X).
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| 27. |
Aguilar-Salinas CA et al. (2001) Early-onset type 2 diabetes: metabolic and genetic characterization in the mexican population.
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| 28. |
None (2001) Mutations in the human genes encoding the transcription factors of the hepatocyte nuclear factor (HNF)1 and HNF4 families: functional and pathological consequences.
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| 29. |
Yoshiuchi I et al. (2001) Analysis of a non-functional HNF-1alpha (TCF1) mutation in Japanese subjects with familial type 1 diabetes.
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| 30. |
Collet C et al. (2002) Prevalence of the missense mutation Gly574Ser in the hepatocyte nuclear factor-1alpha in Africans with diabetes.
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| 31. |
Bluteau O et al. (2002) Bi-allelic inactivation of TCF1 in hepatic adenomas.
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| 32. |
OMIM.ORG article Omim 142410
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| 33. |
Orphanet article Orphanet ID 158583
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| 34. |
NCBI article NCBI 6927
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| 35. |
Wikipedia article Wikipedia EN (HNF1A)
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