The assay covers 12 mutations in the HFE gene
(V53M, V59M, H63D, H63H, S65C, Q127H, P160delC, E168Q, E168X, W169X, C282Y, Q283P)
four mutations in the TFR2 gene
( E60X, M172K, Y250X, AVAQ594-597del) and 2 mutations in the FPN1 gene (N144H, V162del).
Hereditary haemochromatosis (HH) is a very common autosomal recessive disorder of iron metabolism. Among individuals of Northern European descent the carrier frequency is estimated 1 in 10, resulting in up to 1 in 200 homozygous subjects being predisposed to develop the disease. HH is characterized by progressive accumulation of iron in various organs (liver, heart, pancreas), ultimately leading to liver cirrhosis, diabetes, arthritis, cardiomyopathies and premature death. A number of point mutations within a novel MHC class I-like gene (HFE) have been identified and related to HH. Homozygosity for C282Y is observed in the majority of Caucasian HH patients, but other HFE mutations have been identified in HH families. More recently, mutations in the genes encoding transferrin receptor-2 (TFR2) and ferroportin (FPN1) have been found in individuals with non-HFE haemochromatosis. Molecular genetic testing for HH-associated mutations is considered valuable for carrier identification, as well as for presymptomatic diagnosis of the disease. With early detection and simple and very effective treatment by therapeutic bleeding (phlebotomy) in order to remove the iron overload, irreversible organ damage can be completely prevented and survival of patients is virtually normal.