title: Hemochromatosis (HFE) gene sequence analysis of formalin-fixed, paraffin-embedded liver biopsy specimens.
abstract: BACKGROUND
  Hereditary hemochromatosis (HH) is a common disease predominantly characterized by mutations of the HFE gene.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cellular Pathology and Genetics, Armed Forces Institute of Pathology, Washington, DC, USA. przygodz@afip.osd.mil
authors.forename: R M
authors.initials: RM
authors.lastname: Przygodzki
authors.forename: Z D
authors.initials: ZD
authors.lastname: Goodman
authors.forename: L
authors.initials: L
authors.lastname: Rabin
authors.forename: J A
authors.initials: JA
authors.lastname: Centeno
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: A E
authors.initials: AE
authors.lastname: Hubbs
authors.forename: T J
authors.initials: TJ
authors.lastname: O'Leary
mesh_terms: D000367:Age Factors; D003062:Codon / Q000235:genetics; D005260:Female; D005557:Formaldehyde / Q000378:metabolism; D005820:Genetic Testing / Q000379:methods; D006432:Hemochromatosis / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000473:pathology*; D008297:Male; D009154:Mutation / Q000235:genetics; D016612:Paraffin Embedding / Q000379:methods; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods*; D012737:Sex Factors; D016707:Tissue Fixation / Q000379:methods
chemical_list: D003062:Codon; D005557:Formaldehyde; D007501:Iron