46,XX, INV(6)(P21.1P23) IN A PEDIGREE WITH HEREDITARY HEMOCHROMATOSIS

Hereditary haemochromatosis (HFE) is a recessive genetic disease of ir on overload which has been shown by linkage analysis to reside on the short arm of chromosome 6, close to the major histocompatibility compl ex (MHC). Positional cloning of the putative HFE locus has been hamper ed, in part, by the lack of a structural alteration on Gp. In this rep ort, we describe a pedigree with HFE which carries a balanced paracent ric inversion of chromosome 6, inv(6)(p21.1p23), a rarely reported chr omosomal rearrangement in this region. We have determined the inherita nce of the chromosome harbouring the inversion, which segregates as an HFE chromosome. Because the HFE locus has been mapped distal to the H LA-F class I locus at 6p21.3, the breakpoints associated with this chr omosomal rearrangement may provide a significant genomic landmark for positional cloning of the HFE gene.