Albertine Donker

Chapter 5 200 Indeed, Genome Wide Association Studies (GWAS) have identified the 736A variant to be associated with relatively increased iron status biomarkers, red blood cell count, Hb and erythrocyte indices. 8-10 This variant was found to explain ± 2 % in the variation of serum iron and TS and ± 1% in the variation of Hb en MCV in an adult Australian twin cohort. 8 The 253E variant in TMPRSS6 has not been functionally assessed but bio-informatics tools predicted this polymorphism as non-pathogenic (SIFT, Polyphen). In one GWAS the 253E variant has been found to be in modest linkage disequilibrium with V736A and to be associated with a modest decrease in serum iron markers. 10 Therefore, we argue that it is not very likely that the clinical phenotype of the child can be explained by the described genotype. We recommend investigating other causes of inherited and acquired microcytic anemia, especially anemia of chronic disease due to an underlying inflammatory condition.