MOLECULAR-GENETICS OF HEMOCHROMATOSIS

Hemochromatosis is an inherited iron-storage disorder which can cause fatal complications such as heart failure and hepatocellular carcinoma in the abscence of early diagnosis and treatment. In Brittany, France , hemochromatosis is the most common of all genetic diseases, with a g ene prevalence of 0.06. The biochemical abnormality caused by the defe ctive gene is unknown. Excessive duodenal absorption of iron has been demonstrated but may or may not be the primary event. The gene has not yet been identified but has been mapped to the short arm of chromosom e 6, in the area of the major histocompatibility complex, probably wit hin one centimorgan of the HLA-A locus. None of the genes coding for p roteins known to be involved in the metabolism of iron are located in this area. The authors are currently seeking to identify the hemochrom atosis gene using a reverse genetic approach called positional cloning . The characterization of new polymorphic markers and linkage disequil ibrium analysis showed that the gene is located within 350 kb of the H LA-A gene. A search for structural genes present in this area found se ven new genes which have been accurately localized. Structural analysi s of these genes is now being performed to look for an anomaly associa ted with hemochromatosis.