GDF6encodes growth differentiation factor 6, a member of the bone morphogenetic protein (BMP) family within the transforming growth factor beta (TGF-β) superfamily of ligands. The GDF6 sequence consists of three domains, including a signal peptide, a propeptide/prodomain, and a mature receptor-binding TGF-domain. The prodomain of TGF-β ligands is known to regulate the synthesis, extracellular localization, and activity of these proteins. Interestingly, 74% of the GDF6variants detected in patients affect amino acids located in the prodomain of the GDF6sequence. Reported variants are mainly heterozygous missense variants, although other variant types have also been described. Disease mechanisms appear to include altered protein function and disturbed developmental signaling. Molecular diagnosis can be established by targeted sequencing, multigene panels, exome sequencing, or genome sequencing depending on the clinical context.
GDF6