Exclusion of ZIRTL as Candidate Gene of Juvenile Hemochromatosis and Refinement of the Critical Interval on 1q21

Hemochromatosis type 2 (HFE2) or juvenile hemochromatosis (JH) is a rare recessive disorder that causes iron overload, characterized by early onset and severe clinical course. The JH locus maps to chromosome 1q, in a 4-cM region encompassing markers D1S442 and D1S2347. Recently a gene named ZIRTL has been characterized and mapped to 1q21. This gene belongs to a family of divalent metal ion-transporting genes that encode for proteins involved in transport of different metals, including iron. Thus, the ZIRTL gene represents a positional and functional candidate for JH. Here we further restrict the candidate region through segregation analysis of two new polymorphic markers and haplotype analysis in JH families. Furthermore, we exclude ZIRTL as a JH candidate gene showing that it maps outside the critical interval and that its genomic sequence is normal in three patients.