Investigation of BMP6 mutations in Brazilian patients with iron overload.

Background: Iron overload (IO) is a complex condition in which clinical, behavioral and genetic factors contribute to the phenotype. In multiethnic and non-Caucasian populations, mutations in HFE gene alone cannot explain IO in most of the cases, and additional genetic and environmental factors must be investigated. Bone Morphogenetic Proteins (BMPs) play a central role in iron homeostasis by modulating HAMP transcription through the signaling pathway that includes SMAD and HJV. In this study, we aimed to explore the clinical relevance of BMP6 mutations in a cohort of Brazilian patients with IO.

Methods: 41 patients with IO were evaluated. Blood samples were collected to analyze BMP6 mutations through New Sequence Generations (NGS). Frequency of variants and mutations were analyzed and correlated with clinical and environmental characteristics.

Results: We identified BMP6 mutations in three patients with IO. The p.Arg257His mutation was identified in two patients and the p.Leu71Val mutation was identified in one patient. Two of these patients had additional risk factors for IO (HFE mutations and diabetes mellitus).

Conclusion: BMP6 mutations, when combined to other genetic and clinical risk factors, may contribute to IO. Functional studies and THE evaluation of large cohorts are necessary to fully address BMP6 role in IO.