Genotyping as a diagnostic aid in genetic haemochromatosis

Background: Two mutations in a newly described gene, HFE, have been proposed as genetic markers for the inherited iron overload disease, genetic haemochromatosis. Methods: We assessed the frequency of both mutations in a cohort of genetic haemochromatosis patients and compared these with a control population. The patients were genetic haemochromatosis patients from Western Australia whose diagnosis met strict criteria for phenotypic expression. Control patients had other liver disease where iron overload was excluded. Results: Genomic DNA of 72 genetic haemochromatosis patients and 69 controls was examined for the C282Y and H63D mutations of the HFE gene using polymerase chain reaction amplification and restriction enzyme digestion. In genetic haemochromatosis patients, the C282Y mutation was homozygous in 64 of 72, giving a sensitivity of 89% (95% confidence interval 82–96%), heterozygous in five (7%) and absent in another three (4%), whereas none of the control subjects were homozygous. The H63D mutation was present in one genetic haemochromatosis patient and was not useful as a diagnostic marker. In this cohort of Western Australian patients with phenotypic expression of genetic haemochromatosis, the specificity of a homozygous C282Y mutation for genetic haemochromatosis was 100%. Conclusions: The results indicate that genotyping for the C282Y mutation is a useful test for the diagnosis of genetic haemochromatosis in clinical practice.