Haemochromatosis: automated detection of the two point mutations in the HFE gene: Cys282Tyr and His63Asp

Clin Chem Lab Med. 2000 Dec;38(12):1225-30. doi: 10.1515/CCLM.2000.193.

Abstract

Hereditary haemochromatosis (HH) is one of the most common inherited diseases among Caucasians. Two mutations in the HFE gene have been implicated in HH: 80 to 90% of the patients with HH are homozygous for the point mutation CYS282Tyr, while the majority of the remaining patients displays either a compound heterozygosity for the mutation CYS282Tyr and the point mutation HIS63Asp, or are homozygous for HIS63Asp. Though the disease can be treated easily, symptoms are non-specific, and onset and severity are influenced by environmental factors, and therefore the disease can remain undetected until decades of iron overload lead to irreversible damage in a variety of organs, which may result in their failure. In order to detect patients with HH, simple and cost-effective tests are needed. We have developed a rapid, automated, PCR-based test which makes use of a diagnostic restriction site in each of two amplified fragments. The test employs off-the-shelf chemistry and uses the automated detection process of an immunoassay analyzer that is available in many clinical laboratories, thus avoiding an additional investment in a more specialized PCR analyzer. Because of its low costs and easy handling, the assay is particularly suited for the routine clinical laboratories.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartic Acid / chemistry
  • Cysteine / chemistry
  • DNA Mutational Analysis
  • HLA Antigens / genetics*
  • Hemochromatosis / diagnosis*
  • Hemochromatosis / genetics*
  • Hemochromatosis Protein
  • Heterozygote
  • Histidine / chemistry
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Membrane Proteins*
  • Mutation
  • Point Mutation*
  • Polymerase Chain Reaction / economics
  • Polymerase Chain Reaction / instrumentation
  • Polymerase Chain Reaction / methods
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tyrosine / chemistry

Substances

  • HFE protein, human
  • HLA Antigens
  • Hemochromatosis Protein
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Aspartic Acid
  • Tyrosine
  • Histidine
  • Cysteine