Genotyping as a diagnostic aid in genetic haemochromatosis

Background: Two mutations in a newly described gene, HFE, have been propose d as genetic markers for the inherited iron overload disease, genetic haemo chromatosis. Methods: We assessed the frequency of both mutations in a cohort of genetic haemochromatosis patients and compared these with a control population. Th e patients were genetic haemochromatosis patients from Western Australia wh ose diagnosis met strict criteria for phenotypic expression. Control patien ts had other liver disease where iron overload was excluded. Results: Genomic DNA of 72 genetic haemochromatosis patients and 69 control s was examined for the C282Y and H63D mutations of the HFE gene using polym erase chain reaction amplification and restriction enzyme digestion. In gen etic haemochromatosis patients, the C282Y mutation was homozygous in 64 of 72, giving a sensitivity of 89% (95% confidence interval 82-96%), heterozyg ous in five (7%) and absent in another three (4%), whereas none of the cont rol 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 geneti c haemochromatosis, the specificity of a homozygous C282Y mutation for gene tic 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 pr actice. (C) 1999 Blackwell Science Asia Pty Ltd.