Figure 2. The skin phenotype is caused by the biallelic deficiency to γ-carboxylate GRP
(a-c) γ-Carboxylation dose-response curves of GRP and MGP measured by ELISA. The y-axis represents normalized γ-carboxylation (%) to wt. The x-axis represents K1 concentrations [0.1-100 µM]. Error bars depict SD of triplicate measurements of n = 3 experiments. In each figure dose-response curve for GGCX wt is depicted in black. (a) γ-Carboxylation values of GRP and MGP with respect to pathogenic GGCX variant reported in patients having a PXE-like phenotype. These variants were found to be compound heterozygous, where the other allele harbors a nonsense or loss-of-function variant. Compound heterozygous pathogenic variants are represented by the same color with each allele variant represented in solid and dotted line. (b) γ-Carboxylation dose-response curves of GRP and MGP with respect to variants reported to be compound heterozygous in a patient with a mild skin phenotype. (c) γ-Carboxylation dose-response curves of GRP and MGP with respect to variants that did not respond well to K1 administration. Patients harboring these pathogenic variant are expected to develop a skin phenotype later in life.