Genomics of iron refractory iron deficiency anemia phenotype reveals a spectrum of novel pathogenic biallelic and monoallelic TMPRSS6 variants and rare overlapping disorders

Abstract

The study highlights genomic findings in a series of 13 IRIDA phenotype cases. All had microcytic hypochromic anemia with suboptimal oral iron response to two different oral iron preparations at 4–6 weeks and low-normal ferritin, low transferrin saturation, and inappropriately high hepcidin. Targeted NGS on a 26-gene iron panel revealed pathogenic TMPRSS6 variants in 5/13 (38 %) cases. In addition, 2 (15 %) cases revealed rare SMAD4 and TBXAS1 gene variants that can present with refractory anemia but were consistent with diagnosis of hereditary hemorrhagic telangiectasia and Ghosal hematodiaphyseal dysplasia respectively.