We read with great interest the recent publication by Daher et al1 reporting variants in the pro-peptide of BMP6 in patients with iron overload. After identification, they attribute the iron loading phenotype to the variants, based on a series of in vitro overexpression assays. Although the in vitro evidence presented seems to demonstrate alterations in localization of variant BMP6 proteins and subsequent effects on hepcidin induction, we would like to highlight our concerns and the contrast between these results and real-world data from population statistics, the lack of genotype–phenotype segregation, and the high variability in phenotype.

We read with great interest the recent publication by Daher et al1 reporting variants in the pro-peptide of BMP6 in patients with iron overload. After identification, they attribute the iron loading phenotype to the variants, based on a series of in vitro overexpression assays. Although the in vitro evidence presented seems to demonstrate alterations in localization of variant BMP6 proteins and subsequent effects on hepcidin induction, we would like to highlight our concerns and the contrast between these results and real-world data from population statistics, the lack of genotype–phenotype segregation, and the high variability in phenotype.