DNA testing for haemochromatosis: Diagnostic, predictive and screening implications

Since 1996, the identification of the HFE gene has enabled DNA testing for hereditary haemochromatosis (HH). The range of DNA testing available includ es: (1) diagnostic, (2) predictive (also called presymptomatic testing) and (3) screening. Access to DNA testing has been facilitated by an Australian Medicare rebate, the first available for genetic disorders. Despite the av ailability of HFE DNA testing in HH, it remains necessary to interpret resu lts in the context of the clinical picture. Traditional markers based on ph enotype (transferrin saturation, ferritin and liver biopsy) are still requi red in some circumstances. We report our experience with HFE DNA testing us ing a semi-automated approach, which allows multiplexing for the two common mutations (C282Y and H63D). Screening a cohort of beta -thalassaemia major and sickle cell anaemia patients of predominantly Mediterranean origin sho wed that these individuals do not have the common C282Y mutation. This excl uded C282Y as a factor in the pathogenesis of iron overload in these haemog lobinopathies. It also showed that the C282Y mutation is of limited value w hen investigating HH in certain ethnic groups. An Australian family studied illustrated the relative contribution of C282Y and H63D in iron overload. A recently reported third mutation (S65C) in the HFE gene was detected in a low frequency in the populations tested.