Phenotypic and functional data confirm causality of the recently identified hemojuvelin p.r176c missense mutation.

In the present study, we correlate homozygosity for the very recently identified HJV p.R176C substitution with a juvenile hemochromatosis phenotype. We also show that the p.R176C variant fails to up-regulate the hepcidin promoter activity. Altogether, our results definitively show the R176C amino-acid change to be a novel hemojuvelin loss-of-function mutation.