Contiguous gene deletion in HFE2 region (1q21.1) and pathogenic HFE2 mutations in a Chinese hereditary hemochromatosis patient

Juvenile hemochromatosis is caused by the defects of HFE2 gene, located on chromosome 1q with clinical manifestations of iron overload and affected organ damage before adulthood. The present study reports a Chinese juvenile hemochromatosis patient with severe iron overload and unique genetic defects. Gene sequencing results revealed a missense mutation (Q6H) and a nonsense mutation (C321X) in the HFE2 gene of the proband and his father, while another missense mutation (E3D) was identified in his mother. In addition, a gross deletion (about 400 kilobasepairs) was demonstrated in the other HFE2 allele of the proband. We conclude that the gross deletion, combined with the two deleterious point mutations, resulted in a severe hemochromatosis phenotype in the patient.