Transcription factor HNF1alpha

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.

Epidemiology

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.

Gene Structure

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.

Phenotype

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.

Pathology

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.

Test Strategy

Patients with family history and laboratory data suspect for MODY diabetes. Screening of family member in a known MODY family.

Interpretation

The detection of a mutation in this gene is a prerequisite for the diagnosis.

Genetests:

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

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