Alternative titles; symbols
SNOMEDCT: 719974003; ORPHA: 225123; DO: 0111030;
Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
---|---|---|---|---|---|---|
7q22.1 | Hemochromatosis, type 3 | 604250 | Autosomal recessive | 3 | TFR2 | 604720 |
A number sign (#) is used with this entry because of evidence that hemochromatosis type 3 (HFE3) is caused by homozygous or compound heterozygous mutation in the transferrin receptor-2 gene (TFR2; 604720) on chromosome 7q22.
For general background information and a discussion of genetic heterogeneity of hereditary hemochromatosis, see 235200.
Camaschella et al. (1999) described 2 iron-loaded sibs from a consanguineous Italian family. Both had a severe phenotype. The first sib presented with amenorrhea at age 31; liver biopsy and treatment were performed at age 36. In the second sib, decreased libido and impotence at age 21 were the first manifestations of the disease. He had latent diabetes. Cirrhosis was present in both. Serum ferritin was approximately 3,000 microg/liter in both.
Using linkage analysis in a large consanguineous Sicilian family, Camaschella et al. (2000) demonstrated that the HFE3 locus was at chromosome 7q22, with a maximum lod score of 4.09 at theta = 0.0 for markers D7S477 and D7S647.
Camaschella et al. (2000) identified a tyr-to-ter substitution at codon 250 of the TFR2 gene (604720.0001) in 2 Sicilian families segregating HFE3, one consanguineous.
Mattman et al. (2002) studied a group of hemochromatosis patients without a C282Y mutation in the HFE gene (613609.0001) and identified several sequence variants, including a homozygous missense mutation in the transferrin receptor-2 gene (604720.0005).
Griffiths and Cox (2000) reviewed the molecular pathophysiology of iron metabolism.
Camaschella, C., Fargion, S., Sampietro, M., Roetto, A., Bosio, S., Garozzo, G., Arosio, C., Piperno, A. Inherited HFE-unrelated hemochromatosis in Italian families. Hepatology 29: 1563-1564, 1999. [PubMed: 10216143] [Full Text: https://doi.org/10.1002/hep.510290509]
Camaschella, C., Roetto, A., Cali, A., De Gobbi, M., Garozzo, G., Carella, M., Majorano, N., Totaro, A., Gasparini, P. The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nature Genet. 25: 14-15, 2000. [PubMed: 10802645] [Full Text: https://doi.org/10.1038/75534]
Griffiths, W., Cox, T. Haemochromatosis: novel gene discovery and the molecular pathophysiology of iron metabolism. Hum. Molec. Genet. 9: 2377-2382, 2000. [PubMed: 11005792] [Full Text: https://doi.org/10.1093/hmg/9.16.2377]
Mattman, A., Huntsman, D., Lockitch, G., Langlois, S., Buskard, N., Ralston, D., Butterfield, Y., Rodrigues, P., Jones, S., Porto, G., Marra, M., De Sousa, M., Vatcher, G. Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation. Blood 100: 1075-1077, 2002. [PubMed: 12130528] [Full Text: https://doi.org/10.1182/blood-2002-01-0133]