Tippairote, T., Bjørklund, G., Peana, M., & Roytrakul, S. (2020). The Proteomics Study of Compounded HFE/TF/TfR2/HJV Genetic Variations in a Thai Family with Iron Overload, Chronic Anemia, and Motor Neuron Disorder. Journal of Molecular Neuroscience. doi:10.1007/s12031-020-01676-8
The findings of unusual compound genetic variants of HFE/TF/TfR2/HJV genes with the confirmation of proteomic study produced the clinical pictures of iron overload and hypochromic microcytic anemia. These phenotypes were the consequences of impaired TF/TfR functions, poor uptake of iron into erythroblast precursors, and enhanced TfR-independent uptake of iron in other tissues while depleting the erythropoiesis iron supply. At a later stage, without signs
of hepcidin-suppressed ferroportin activity, the defective TfR-related BMP/SMAD/HAMP signaling promoted the intracellular iron overload and the worsening clinical outcomes. The collective spectrum of these clinical phenotypes could span from the mild to moderate symptoms of chronic anemia to the diagnosed motor neuron disease.