2. Academic Validation
  3. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis

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

  • Nat Genet. 1996 Aug;13(4):399-408. doi: 10.1038/ng0896-399.
J N Feder 1,  A Gnirke,  W Thomas,  Z Tsuchihashi,  D A Ruddy,  A Basava,  F Dormishian,  R Domingo Jr,  M C Ellis,  A Fullan,  L M Hinton,  N L Jones,  B E Kimmel,  G S Kronmal,  P Lauer,  V K Lee,  D B Loeb,  F A Mapa,  E McClelland,  N C Meyer,  G A Mintier,  N Moeller,  T Moore,  E Morikang,  C E Prass,  L Quintana,  S M Starnes,  R C Schatzman,  K J Brunke,  D T Drayna,  N J Risch,  B R Bacon,  R K Wolff
Affiliations

Affiliation

  • 1 Mercator Genetics, Inc., Menlo Park, California 94025, USA.
PMID: 8696333 DOI: 10.1038/ng0896-399
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 I-like proteins in iron metabolism.

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