ClinVar

In a female patient with a novel connective tissue disorder (BCARD; 612394), Salo et al. (2008) identified compound heterozygosity for 2 mutations in the PLOD3 gene: a 668A-G transition resulting in an asn223-to-ser (N223S) substitution in the region of the glycosyltransferase (GT/GTT) domain, and a 1-basepair deletion (2071delT; 603066.0002). The 2071delT mutation results in a translational frameshift, generating a premature translation stop codon (Cys691AlafsTer9). This mutated allele produces a protein truncated by 40 amino acids and deviates from the LH3 sequence in the last 8 C-terminal amino acids. The missense mutation was inherited from the father, and the deletion from the mother. Enzyme activity assays of recombinant LH3 with the N223S mutation demonstrated substantially reduced collagen GT and GTT activities of LH3 and also reduced LH activity to approximately half of normal levels. Enzyme activity assays of recombinant LH3 with the frameshift mutation resulted in complete loss of the LH activity for LH3 as well as reduced collagen GT and GTT activities.