Definition

The HFE gene encodes a cell surface protein that regulates iron absorption and storage. The two main variants leading to hemochromatosis act through different mechanisms: C282Y severely disrupts iron regulation by preventing the protein from reaching the cell surface; H63D only mildly alters the protein's structure and rarely causes clinical hemochromatosis on its own (homozygous).

Gene/region examined

HFE - H63D, HFE - C282Y, HFE - S65C

Method

Sequence analysis

Accepted sample types

EDTA blood, AF, CVS

Inheritance

Autosomal recessive, but with low penetrance; most C282Y homozygotes do not develop clinical HFE hemochromatosis. Longitudinal studies have reported elevated ferritin in 38 to 50% of homozygotes and clinical disease in 10 to 33%.

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Inheritance Patterns

Describes how a genetic condition is passed on within a family. There are five main patterns

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Carrier (Heterozygous / Homozygous)

Why it matters: In autosomal recessive inheritance, when each parent is a carrier (while both appear healthy), the chance of their child being born with the disease is 25% in each

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VUS (Variant of Uncertain Significance)

This is the situation where the test has detected a change in the DNA, but the role of this change in the development of disease is unconfirmed.

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How to Read a Genetic Test Result (Positive / Negative / VUS)

A genetic test result falls into three main categories

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Types of Genetic Tests

A genetic test is a type of medical test that detects changes in genes, chromosomes or proteins. Today there are more than 77,000 genetic tests available.

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