Hemochromatosis and “HLA-H”: Definite!

✍ Scribed by E C Jazwinska; L W Powell

• Book ID: 102242914
• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 162 KB
• Volume: 25
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510250240

✦ Synopsis

Hereditary hemochromatosis (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 250kb 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 hemochromatosis is supported by the frequency and nature of the major mutation and prior studies implicating MHC class I-like proteins in iron metabolism.