Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation

• Published in: Blood 2002-08, Vol.100 (3), p.1075-1077
• Main Authors: MATTMAN, Andre, HUNTSMAN, David, MARRA, Marco, DE SOUSA, Maria, VATCHER, Greg, LOCKITCH, Gillian, LANGLOIS, Sylvie, BUSKARD, Noel, RALSTON, Diana, BUTTERFIELD, Yaron, RODRIGUES, Pedro, JONES, Steven, PORTO, Graca
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Canada - epidemiology; DNA Mutational Analysis; Family Health; Female; Genetic Predisposition to Disease; Genotype; Hemochromatosis - genetics; Hemochromatosis Protein; Histocompatibility Antigens Class I - genetics; HLA Antigens - genetics; Humans; Iron Overload - genetics; Male; Medical sciences; Membrane Proteins; Metabolic diseases; Metals (hemochromatosis...); Other metabolic disorders; Pedigree; Receptors, Transferrin - genetics
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-01-0133

Hereditary hemochromatosis (HH) is classically associated with a Cys282Tyr (C282Y) mutation of the HFE gene. Non-C282Y HH is a heterogeneous group accounting for 15% of HH in Northern Europe. Pathogenic mutations of the transferrin receptor 2 (TfR2) gene have been identified in 4 Italian pedigrees with the latter syndrome. The goal of this study was to perform a mutational analysis of the TfR2 and HFE genes in a cohort of non-C282Y iron overload patients of mixed ethnic backgrounds. Several sequence variants were identified within the TfR2 gene, including a homozygous missense change in exon 17, c2069 A-->C, which changes a glutamine to a proline residue at position 690. This putative mutation was found in a severely affected Portuguese man and 2 family members with the same genotype. In summary, pathologic TfR2 mutations are present outside of Italy, accounting for a small proportion of non-C282Y HH.