Significance of linkage disequilibrium between mutation C282Y and a MseI polymorphism in population screening and DNA diagnosis of hemochromatosis

An increasing number of studies demonstrate a lack of phenotypic expression in subjects found to be homozygous for the common hereditary hemochromatos is (HH) mutation, C282Y In this study the impact of possible overestimation of C282Y homozygosity, as a consequence of a MseI polymorphism identified in intron 4 of the HFE gene, was investigated in South African subjects. Ut ilization of a modified polymerase chain reaction (PCR)-based assay highlig hted the potential implications with respect to genotype/phenotype correlat ion studies, particularly in the general population. Mistyping rather than lack of disease association provides a plausible explanation for the phenom enon of C282Y homozygosity without iron overload. Reassessment of C282Y mut ation status in such cases may result in justified population screening in HH.