Genetic heterogeneity underlies juvenile hemochromatosis phenotype: analysis of three families of northern Greek origin.

Hereditary hemochromatosis is a genetically heterogeneous disease. Common HFE mutations (C282Y and H63D) are related to the majority of hereditary hemochromatosis cases in populations of Northern European ancestry (HFE1). Juvenile hemochromatosis (JH) is a more severe iron overload disorder, usually presenting at the second decade of life. The gene responsible for JH lies on a genetic locus at chromosome 1q. We have performed a genetic linkage study in three families of Northern Greek origin with typical clinical features of JH. In two families results were in accordance with linkage to chromosome 1q. In one family linkage of the disease to the genetic loci at 1q21, 7q22, and 6p22 was excluded. We suggest that more than one gene may underlie the JH phenotype. This genetic type of hemochromatosis may be designated 1q unlinked juvenile hemochromatosis. Family studies are necessary to establish the genetic diagnosis of JH.