New Mutations in HFE2 and TFR2 Genes Causing Non HFE-Related Hereditary Hemochromatosis

Abstract

Hereditary hemochromatosis (HH) is an iron metabolism disease clinically characterized by excessive iron deposition in parenchymal organs such as liver, heart, pancreas, and joints. It is caused by mutations in at least five different genes. HFE hemochromatosis is the most common type of hemochromatosis, while non-HFE related hemochromatosis are rare cases. Here, we describe six new patients of non-HFE related HH from five different families. Two families (Family 1 and 2) have novel nonsense mutations in the HFE2 gene have novel nonsense mutations (p.Arg63Ter and Asp36ThrfsTer96). Three families have mutations in the TFR2 gene, one case has one previously unreported mutation (Family A—p.Asp680Tyr) and two cases have known pathogenic mutations (Family B and D—p.Trp781Ter and p.Gln672Ter respectively). Clinical, biochemical, and genetic data are discussed in all these cases. These rare cases of non-HFE related hereditary hemochromatosis highlight the importance of an earlier molecular diagnosis in a specialized center to prevent serious clinical complications.

A Novel Mutation of Transferrin Receptor 2 in a Chinese Pedigree With Type 3 Hemochromatosis: A Case Report

“…In recent years, increasing mutations in the TFR2 gene which are related to type 3 HH have been documented (Hernández et al, 2021;Joshi et al, 2015). As shown in Supplementary Table S1, a total of 33 pathogenic TFR2 mutations associated with HH have been described in the Human Gene Mutation Database (Stenson et al, 2020).…”