Hemochromatosis (HFE) gene sequence analysis of formalin-fixed, paraffin-embedded liver biopsy specimens

Mol Diagn. 2001 Dec;6(4):227-32. doi: 10.1054/modi.2001.29165.


Background: Hereditary hemochromatosis (HH) is a common disease predominantly characterized by mutations of the HFE gene.

Methods and results: We investigated the utility of HFE gene sequence analysis in the diagnosis of HH in 61 prospectively accrued formalin-fixed, paraffin-embedded liver biopsy specimens with clinical or histologic features suggestive of HH. Mutations in codons 63 or 282 of the HFE gene were identified by direct sequencing; in 21 of these samples, quantitative hepatic iron testing was also performed. Changes characteristic of HH were present in 16 (26%) of the cases, and 54% of the cases showed HFE gene mutations. The most common alteration was homozygous mutation of codon 282 (11 cases, 18%), followed by the combined 63 + 282 heterozygous mutation (3 cases, 5%). Two cases (3%) showed biallelic mutation of codon 63. The other 28 cases (46%) showed no sequence abnormalities. Weak iron staining did not exclude HH; intense staining did not reliably predict HH.

Conclusion: When HH is clinically and/or histologically suspected, HFE gene sequencing of formalin-fixed, paraffin-embedded liver biopsy specimens is a rapid and cost-effective approach to genotypic diagnosis of HH.

MeSH terms

  • Age Factors
  • Codon / genetics
  • Female
  • Formaldehyde* / metabolism
  • Genetic Testing / methods
  • Hemochromatosis / genetics*
  • Hemochromatosis / pathology*
  • Humans
  • Iron / metabolism
  • Liver / chemistry
  • Liver / pathology*
  • Male
  • Mutation / genetics
  • Paraffin Embedding* / methods
  • Prospective Studies
  • Sensitivity and Specificity
  • Sequence Analysis, DNA / methods*
  • Sex Factors
  • Tissue Fixation* / methods


  • Codon
  • Formaldehyde
  • Iron