Juvenile hemochromatosis locus maps to chromosome 1q

Juvenile hemochromatosis (JH) is an autosomal recessive disorder that leads to severe iron loading in the 2d to 3d decade of life. Affected members in families with JH do not show linkage to chromosome 6p and do not have muta tions in the HFE gene that lead to the common hereditary hemochromatosis. I n this study we performed a genomewide search to map the JH locus in nine f amilies: six consanguineous and three with multiple affected patients. This strategy allowed us to identify the JH locus on the long arm of chromosome 1. A maximum LOD score of 5.75 at a recombination fraction of 0 was detect ed with marker D1S498, and a LOD score of 5.16 at a recombination fraction of 0 was detected for marker D1S2344. Homozygosity mapping in consanguineou s families defined the limits of the candidate region in an similar to 4-cM interval between markers D1S442 and D1S2347. Analysis of genes mapped in t his interval excluded obvious candidates. The JH locus does not correspond to the chromosomal localization of any known gene involved in iron metaboli sm. These findings provide a means to recognize, at an early age, patients in affected families. They also provide a starting point for the identifica tion of the affected gene by positional cloning.