Albertine Donker

Chapter 9 314 Therefore, in our opinion, Dutch legislation regarding minimal-risk pediatric research needs relaxation, especially of the informed consent procedure. In the interest of children, we highly agree with the following recent statement in the Lancet: ‘The time has come to protect children and young people through research, not from research’. 61 High-throughput DNA sequencing technology in the field of iron disorders holds significant promise for the future Since the use of traditional diagnostic approaches was also an important limitation of our studies, a next suggestion to strengthen future research would be the wider application of NGS, especially WES, in patients with (suggested) microcytic anemias due to genetic disorders of iron metabolism or heme synthesis. As mentioned above, WES might shed new light on the phenotypic and genotypic spectrum of particular diseases. Importantly, various studies have shown a high concordance with Sanger sequencing, making WES non-inferior and potentially even more accurate than the classical sequencing techniques. 62,63 During the last decades, enormous progress has been made in the mapping of genes directly causing diseases or conferring susceptibility to complex disorders in general, 16 also in the field or iron disorders. 18 Apart from WES in patients, genome wide association studies (GWAS) in a broad population have discovered common genetic variants associated with iron metabolism that might confer a susceptibility to iron disorders. 64,65 Although such associations simply represent a statistical relation between specific alleles and phenotypes, which might have various reasons (totally different from the phenomenon of linkage that represents a relation between specific loci e.g. physical sites on the chromosome and phenotypes), GWAS has provided useful insights regarding iron handling, which are helpful in the formulation of hypotheses regarding iron disorders. Good examples are the studies of Traglia 66 and Galesloot, 67 who disproved the hypothesis that the association of common HFE and TMPRSS6 with body iron parameters can be explained by the intermediate effect on hepcidin concentration. By contrast, their data suggest that serum hepcidin independent mechanisms play a role in the association of certain HFE and TMPRRS variants with serum iron parameters. 66,67