Juvenile hemochromatosis is a recessive disorder of iron overload. It results in cardiomyopathy, diabetes and hypogonadism.
Juvenile hemochromatosis has previously been linked to the centromeric region of chromosome 1q.
In this study, researchers identified the positional cloning of the locus associated with juvenile hemochromatosis. They also identified a new gene crucial to iron metabolism.
The team mapped the recombinant interval in families of Greek descent. They identified multiple deleterious mutations in a transcription unit of previously unknown function.
This transcription unit has been called HFE2, and its protein product, hemojuvelin.
|Mutation accounted for two-thirds of the mutations found.|
The team found that 1 mutation accounted for two-thirds of the mutations found.
Dr George Papanikolaou's team determined that HFE2 transcript expression was restricted to liver, heart and skeletal muscle. This was similar to that of hepcidin - a key protein implicated in iron metabolism.
They also found that urinary hepcidin levels were depressed in individuals with juvenile hemochromatosis. This suggested that hemojuvelin is not the hepcidin receptor, but that HFE2 modulates hepcidin expression.