A novel MHC class I–like gene is mutated in patients with hereditary haemochromatosis

JN Feder, A Gnirke, W Thomas, Z Tsuchihashi… - Nature …, 1996 - nature.com
JN Feder, A Gnirke, W Thomas, Z Tsuchihashi, DA Ruddy, A Basava, F Dormishian…
Nature genetics, 1996nature.com
Hereditary haemochromatosis (HH), which affects some 1 in 400 and has an estimated
carrier frequency of 1 in 10 individuals of Northern European descent, results in multi–organ
dysfunction caused by increased iron deposition, and is treatable if detected early. Using
linkage–disequilibrium and full haplotype analysis, we have identified a 250–kilobase
region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that
is identical–by–descent in 85% of patient chromosomes. Within this region, we have …
Abstract
Hereditary haemochromatosis (HH), which affects some 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals of Northern European descent, results in multi–organ dysfunction caused by increased iron deposition, and is treatable if detected early. Using linkage–disequilibrium and full haplotype analysis, we have identified a 250–kilobase region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical–by–descent in 85% of patient chromosomes. Within this region, we have identified a gene related to the MHC class I family, termed HLA–H, containing two missense alterations. One of these is predicted to inactivate this class of proteins and was found homozygous in 83% of 178 patients. A role of this gene in haemochromatosis is supported by the frequency and nature of the major mutation and prior studies implicating MHC class Mike proteins in iron metabolism.
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