PLOD3 encodes the protein lysyl hydroxylase 3 (LH3) that is involved in post-translational modification of collagens. Since LH3 exerts its lysyl hydroxylase and galactosyltransferase activities on multiple collagens, particularly type IV, VI, XI and XII, pathogenic variants in PLOD3 resulting in loss of LH3 activities are predicted to affect a variety of proteins, thus explaining the complex multisystemic features seen in affected individuals.
Pathogenic variants have been identified in the three main domains of LH3 – GT (catalytic glycosyltransferase), AC (accessory glycosyltransferase), and LH (lysyl hydroxylase). A comprehensive summary of the mutations affecting the human PLOD3 gene and their mapping on the three-dimensional structure of LH3 is available at http://fornerislab.unipv.it/SiMPLOD/
Genetic testing is available through some diagnostic laboratories that offer connective tissue disorder (CTD) or eye disorder gene panels, or through genomic (exome or genome) sequencing.