Related Experiment Video
Updated: Jun 23, 2026
03:45
Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
Published on: August 8, 2022
Hemochromatosis: as a conformational disorder
Steven G Gray1, John Crowe, Matthew W Lawless
1Translational Cancer Research Group, Department of Clinical Medicine, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St. James's Hospital, Dublin 8, Ireland.
The International Journal of Biochemistry & Cell Biology
|April 21, 2009
Summary
Hereditary hemochromatosis (HH) is linked to the C282Y mutation in the HFE protein, causing it to misfold and accumulate. This review focuses on these early molecular events, offering new diagnostic and treatment insights.
Area of Science:
- Biochemistry
- Genetics
- Molecular Biology
Background:
- Hereditary hemochromatosis (HH) is an iron overload disorder.
- The most common form is associated with the C282Y homozygous mutation of the hemochromatosis protein (HFE).
- HFE C282Y mutations are increasingly recognized as a conformational disease.
Purpose of the Study:
- To review the upstream molecular events in HFE C282Y hereditary hemochromatosis.
- To explore the consequences of HFE C282Y protein mislocalization and aggregation.
- To identify potential avenues for improved diagnosis and treatment.
Main Methods:
- Literature review focusing on molecular mechanisms.
- Analysis of endoplasmic reticulum (ER) stress pathways.
- Examination of protein conformational changes and cellular retention.
Main Results:
- The HFE C282Y mutant protein aggregates and is retained in the endoplasmic reticulum (ER).
- Misfolded protein accumulation in the ER triggers complex signaling cascades.
- These upstream events precede the end-stage iron overload.
Conclusions:
- Understanding HFE C282Y protein mislocalization is crucial.
- Focusing on early molecular events offers novel therapeutic targets.
- This approach may lead to earlier diagnosis and more effective treatments for HH.
Related Concept Videos
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
01:49Multiple Allele Traits
The Concept of Multiple Allelism
01:31Translation
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
01:31Translation
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
01:27Disorders of Erythrocytes
Disorders of erythrocytes, or red blood cells (RBCs), include a range of conditions affecting their number, shape, or function.
Erythrocyte disorders can be broadly categorized into two main types: anemic and polycythemic conditions.
A low oxygen-carrying capacity of the blood due to the loss, lower production, or destruction of erythrocytes is termed anemia. Hemorrhagic anemia, for example, occurs when bleeding from an external wound or internal ulcer reduces erythrocyte counts.
On the other...
Erythrocyte disorders can be broadly categorized into two main types: anemic and polycythemic conditions.
A low oxygen-carrying capacity of the blood due to the loss, lower production, or destruction of erythrocytes is termed anemia. Hemorrhagic anemia, for example, occurs when bleeding from an external wound or internal ulcer reduces erythrocyte counts.
On the other...
01:43Sex-linked Disorders
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.