Treatment in IRIDA focuses on use of intravenous iron preparations to circumvent oral absorptive defect resulting from high levels of hepcidin due to TMPRSS6 gene variations.
It has recently been proposed that HFE protein could be a potential target of matriptase-2, a hepatocyte protease mutated in iron-refractory iron deficiency anemia.
Our results provide important information about commonly used liver cell models and shed light on the impact of two TMPRSS6 mutations associated with IRIDA.
However, given that only 38% (23/60 cases) of cases with iron refractoriness had IRIDA phenotype, a balanced approach is needed and other causes for refractoriness should be investigated before genetic studies for TMPRSS6 are undertaken.
Iron refractory iron deficiency anemia (IRIDA) is a rare hereditary disease caused by mutations in TMPRSS6 gene encoding Matriptase-2, a negative regulator of hepcidin transcription.
Furthermore, we analyze multiple murine genetic models of iron dysregulation, including β-thalassemia intermedia (Hbb(th3/+)), hereditary hemochromatosis (Hfe(-/-), Hjv(-/-), and Tfr2(Y245X/Y245X)), hypotransferrinemia (Trf(hpx/hpx)), heterozygous transferrin receptor 1 deficiency (Tfrc(+/-)) and iron refractory iron deficiency anemia (Tmprss6(-/-) and Tmprss6(hem8/hem8)).
The discovery that many of these cases harbor mutations in the TMPRSS6 gene led to the recognition that they represent a single clinical entity: iron-refractory iron deficiency anemia (IRIDA).
Sequencing analysis of the TMPRSS6 gene in 21 new IRIDA patients from 16 families with different ethnic origin reveal 17 novel mutations, including the most frequent mutation in Southern Italy (p.W590R).
Presence of high hepcidin suggested a diagnosis of IRIDA, which was eventually confirmed by identification of a novel homozygous mutation, p.Pro354Leu, in the TMPRSS6 gene.
We identified five patients from four independent families displaying the IRIDA picture with truncating biallelic mutations in TMPRSS6, one of which is novel.
Mutations in TMPRSS6 gene cause iron-refractory iron deficiency anemia, a rare autosomal recessive disorder characterized by hypochromic microcytic anemia not responsive to oral iron therapy and partially responsive to parenteral iron administration.
Inactive matriptase-2 mutants found in IRIDA patients still repress hepcidin in a transfection assay despite having lost their serine protease activity.
We herein report a Korean female with IRIDA who was compound heterozygous for two mutations in TMPRSS6: a novel missense mutation c.1807G>C (p.Gly603Arg) in the serine protease domain and a known splicing mutation c.863+1G>T (IVS6+1G>T).
We herein report a Korean female with IRIDA who was compound heterozygous for two mutations in TMPRSS6: a novel missense mutation c.1807G>C (p.Gly603Arg) in the serine protease domain and a known splicing mutation c.863+1G>T (IVS6+1G>T).
Inactive matriptase-2 mutants found in IRIDA patients still repress hepcidin in a transfection assay despite having lost their serine protease activity.
The HRM assay was proved to be rapid, accurate and cost-effective method to identify the TMPRSS6 gene mutations and can be used in the clinical diagnosis of IRIDA.