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
  • 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.