Inheritance Pattern The disease<unk>  is inherited in an autosomal recessive manner. Individuals with this disease exhibit a mutation or pathogenic effect in both copies of the TFR2 in each cell. People with only one copy of TFR2 that is affected are labeled as carriers. Carriers typically do not exhibit signs or symptoms of the disease. This disease is shown to have reduced penetrance. Thus, some people with pathogenic variants of the TFR2 gene may never present symptoms related to the disease. Gene Involved The gene involved with patients diagnosed with type 3 hemochromatosis is TFR2 ( or HFE3). HFE is most often the cause of hereditary hemochromatosis. The HFE gene provides instructions for producing a protein that is located on the surface of cells, primarily liver and intestinal cells. The HFE protein is also found on some immune system cells. The HFE protein interacts with other proteins on the cell surface to detect the amount of iron in the body. When the HFE protein is attached to a protein called transferrin receptor 1, the receptor cannot bind to a protein called transferrin. When transferrin receptor 1 is bound to transferrin, iron enters liver cells. So, it is likely that the HFE protein regulates iron levels in liver cells by preventing transferrin from binding to transferrin receptor 1. The HFE protein regulates the production of a protein called hepcidin. Hepcidin is produced by the liver, and it determines how much iron is absorbed from the diet and released from storage sites in the body. When the HFE protein is not bound to transferrin receptor 1, it binds to a group of other proteins that includes hepcidin. The formation of this protein complex triggers the production of hepcidin. So when the HFE protein is bound to transferring receptor 1, hepcidin production is turned off and when the HFE protein is not bound to transferring receptor 1, hepcidin production is turned on. The transferrin receptor 2 (TFR2) gene is responsible for encoding a single-pass type II membrane protein. This protein mediates cellular uptake of transferrin-bound iron, and may be involved in iron metabolism, hepatocyte function and erythrocyte differentiation. Type of Mutations Majority of the cases of hemochromatosis are caused by mutations in the HFE gene. More specifically, Type 3 HH is characterized by mutations in transferrin receptor 2. HH type 3 is linked to mutations in a gene on chromosome 7q22, encoding TFR2. A deletion in the DNA sequence at this location is associated with causing type 3 hemochromatosis. Location of the Chromosome The heterozygous mutation in the transferrin receptor-2 gene (TFR2) and the mutation in the<unk>  gene (HFE3) are the causes of<unk> . These mutations are found on chromosome 7q22. The location of the genes affected are at 7:100,620,419 on the DNA chromosome. Effects on Gene Products The gene product is a member of the major histocompatibility complex class I-like family and holds a mutation, Cys-292 to Tyr (C282Y), in 85% of patient chromosomes. The mutation eliminates the ability of HFE to prevent cell-surface expression. There are also other mutations that prevent association of the mutant HFE protein with transferrin receptor. Spectrum of Disease Severity The disease can manifest itself without showing any symptoms, but these symptoms can emerge over time and the disease can therefore become more severe. Symptoms that emerge early on in the disease are generally less severe, and may include conditions such as fatigue, weakness, skin discoloration, loss of sex drive and joint pain. Late in the disease, people may experience liver disease as well as disease to other major organs as excess iron is deposited over time. People can also develop diabetes, heart problems, and abdominal pain.
Haemochromatosis type 3
Hereditary haemochromatosis
Hemochromatosis type 4
Juvenile hemochromatosis
Niemann–Pick disease, type C
Wilson's disease
Wilson–Mikity syndrome
Type 3c diabetes