These investigators have ascertained one of the largest collection of pedigrees with hereditary iron overload. Over 300 families have been ascertained. Extensive phenotypic analyses have been completed and genotyping studies have demonstrated that approximately 90% of the pedigrees have iron overload associated with homozygosity for the cysteine 282 tyrosine mutation of the HFE gene. The current focus is to test the hypothesis that hemochromatosis is a disease caused by malregulated cellular iron export. Epstein-Barr Virus (EBV) transformed lymphocytes have been generated from at least one member of every pedigree and an in vitro system has been devised to analyze cellular iron export. The human macrophage model of regulated iron export (based on animal models of genetic iron overload) is also being developed utilizing macrophages isolated from bone marrow aspirations of patients with hemochromatosis associated with the ancestral HFE mutation and those with other mutations of the HFE locus or no HFE associated mutations. These in vitro cell culture models are in developmental state at the present. A large clinical phenotyping study has been completed and demonstrated that approximately half of the patients with hemochromatosis developed disease related morbidity. A manuscript has been submitted describing this study and provided ample documentation that morbidity is a common consequence of homozygosity for hemochromatosis gene mutations, thus justifying large-scale population screening studies.
Showing the most recent 10 out of 535 publications
