6] Human genes: TMPRSS6, transmembrane protease, serine 6; HFE, hemochromatosis; PER1, period homolog 1 (Drosophila); TIMELESS, timeless homolog (Drosophila); CLOCK, clock homolog (mouse); HAMP, hepcidin antimicrobial peptide; TFR2, transferrin receptor 2; HFE2
, hemochromatosis type 2 (juvenile).
Hemojuvelin is a protein encoded by a gene initially named HFE2 but later designated HJV because it is not a member of the HFE family but instead is related to the repulsive guidance molecule family of proteins.
Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis.
Juvenile hemochromatosis (JH) is due to a mutation in 1 of 2 genes: HFE2 [hemochromatosis type 2 (juvenile); also known as HJV and encoding hemojuvelin] (7) and, more rarely, HAMP (hepcidin antimicrobial peptide) (8).
We first targeted HFE and TFR2 genes in group 1A and preferentially screened HAMP and HFE2 genes in group 113.
GenBank sequence accession numbers for the SLC40A1, FTL, HFE, HFE2, HAMP, and TFR2 genes are NC 000002.
We chose amplicons to cover the 39 exons, exon/ intron boundaries, and most of the 5' and 3' UTRs of HFE, TFR2, HFE2, HAMP, and SLC40A1, as well as the 5' UTR of FTL.
We optimized the conditions to apply the method to the 2 main phenotypic profiles: HH/group 1 (HFE, TFR2, HFE2, and HAMP) or HF/ group 2 (SLC40A1 and FTL).
In group 1, 1 patient had a new HFE mutation, 1 patient had a novel HFE2 mutation, and 2 patients had a new SLC40A1 mutation.