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

• Published in: Genes Vol. 12; no. 12; p. 1980
• Main Authors: Hernández, Gonzalo, Ferrer-Cortès, Xenia, Venturi, Veronica, Musri, Melina, Pilquil, Martin Floor, Torres, Pau Marc Muñoz, Rodríguez, Ines Hernandez, Mínguez, Maria Àngels Ruiz, Kelleher, Nicholas J, Pelucchi, Sara, Piperno, Alberto, Alberca, Esther Plensa, Ricós, Georgina Gener, Giró, Eloi Cañamero, Pérez-Montero, Santiago, Tornador, Cristian, Villà-Freixa, Jordi, Sánchez, Mayka
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13-12-2021; MDPI
• Subjects: Adult; Codon, Nonsense - genetics; Female; Genes; GPI-Linked Proteins - genetics; GPI-Linked Proteins - metabolism; Hemochromatosis; Hemochromatosis - genetics; Hemochromatosis - physiopathology; Hemochromatosis Protein - genetics; Hemochromatosis Protein - metabolism; Histocompatibility Antigens Class I - metabolism; Humans; Iron; Iron - metabolism; Liver; Liver - metabolism; Male; Membrane Proteins - genetics; Metabolism; Middle Aged; Mutation; Pancreas; Patients; Pedigree; Proteins; Receptors, Transferrin - genetics; Receptors, Transferrin - metabolism; homozygous; iron overload; TFR2 gene; missense; HFE related hereditary hemochromatosis; non-HFE related hereditary hemochromatosis; HFE2 gene; nonsense
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes12121980

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
gene have novel nonsense mutations (p.Arg63Ter and Asp36ThrfsTer96). Three families have mutations in the
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.