Genetics of Haemochromatosis

“…Removal of iron and the prevention of its reaccumulation by phlebotomy treatment dramatically improves life expectancy in these patients (4)(5)(6)(7). The discovery of a tight linkage between HH and the HLA-A locus has led to the clarification of the genetic nature and the autosomal recessive inheritance of the disease (8,9). A similar disease is not known in animals, and although many attempts have been made to develop an appropriate animal model by dietary application of different iron compounds, severe organ damage as seen in HH could not be reproduced in these models (10).…”

mentioning

confidence: 99%

Defective iron homeostasis in beta 2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man.

Santos¹,

Schilham²,

Rademakers³

et al. 1996

The Journal of Experimental Medicine

181

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Previously, hepatic iron overload resembling that in hereditary hemachromatosis (HH) has been found in beta 2-microglobulin knockout (beta 2m-/-) mice. We have now characterized iron metabolism in beta 2m-/- mice. The mutant mice fail to limit the transfer of iron from mucosal cells into the plasma. Transferrin saturation is abnormally high. Pathologic iron depositions occur predominantly in liver parenchymal cells. Reconstitution with normal hematopoietic cells redistributes the iron from parenchymal to Kupffer cells, but does not correct the mucosal defect. We conclude that (a) iron metabolism is defective in the gut mucosa as well as the liver of beta 2m-/- mice; and (b) a beta 2m-dependent gene product is involved in iron homeostasis. Recently, a novel gene of the major histocompatibility complex class I family, HLA-H, has been found to be mutated in a large proportion of HH patients. Our data provide functional support for the proposed causative role of HLA-H mutations in HH.

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“…Iron parameters are influenced by age, gender, and disease, as well as by biological variation within an individual (36). In the present study, we also considered the frequency of blood donations as a covariate in the statistical analyses of iron parameters (37).…”

Section: Discussionmentioning

confidence: 99%