Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

hemochromatosis gene

Two mutations in this gene, encoding a putative iron transporter, have been associated with hemochromatosis.

Epidemiology

The frequency of homozygous C282Y mutations among patients with hemochromatosis is 52-100%. In our country it is about 90%. The remainder might be mixed heterozygous (C282Y/H63D) about 5%, homozygous (H63D) about 1,5%, heterozygous (C282Y) about 3,6% or heterozygous (H63D).In caucasian population homozygous C282Y mutation is about 0,4% and heterozygous 9,2%.Allelfrequency of H63D mutation is about 22% in Europe. The C282S mutation is extremely rare.

Gene Structure

The gene is about 10kb in size. It is located on chromosome 6 at position 6p21.3. There are 11 splice variants known at this moment. These consists of 3 to 7 exons.

Phenotype

The clinical picture depends on the organ dysfunction when iron overloaded. In liver it causes zirrhosis, in pancread diabetes and in cardiac muscels heart failure. The colour of skin is typical in full blown disease. The diagnosis can be confirmed by histological investigation with iron staining.Interestingly mutations in this gene seem to be a risk factor for life.

Pathology

The protein product of this gene is responsible for iron uptake and removal by the enterocytes. The machanism of its function is not known yet. If this ene is mutated this leads to iron overload in liver, pancreas and heart.

Test Strategy

Patients with clinical and biochemical findings suspect for hemochromatosis.

Interpretation

You can use this test to confirm 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 5 days
Specimen type genomic DNA
Clinic Method Target mutation analysis
Turnaround 20 days
Specimen type genomic DNA
Clinic Method Multiplex Ligation-Dependent Probe Amplification
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Hemochromatosis 1
BMP2
HFE

References:

1.

Hanson EH et al. (2001) HFE gene and hereditary hemochromatosis: a HuGE review. Human Genome Epidemiology.

[^]
2.

None () Frequency analysis and allele map in favor of the celtic origin of the C282Y mutation of hemochromatosis.

[^]
3.

Bathum L et al. (2001) Association of mutations in the hemochromatosis gene with shorter life expectancy.

[^]
4.

NCBI article

NCBI 3077 [^]
5.

OMIM.ORG article

Omim 613609 [^]
6.

Orphanet article

Orphanet ID 123411 [^]
7.

Wikipedia article

Wikipedia EN (HFE_(gene)) [^]
Update: April 29, 2019