PMC8138308_01
Joint hypermobility: (A) Bilateral active hyperextension of the knee; (B) Passive apposition of thumb to forearm; (C) Active hyperextension of elbow.
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PMC8138308_01_fgene-12-640558-g0001.jpg
F1
She showed generalized joint hypermobility scoring 9/9 in the Beighton score (Figures 1A-C) with recurrent joint dislocations, in particular of shoulders, wrist, and knees.
PMC8138308_02
PMC8138308_03
Collagen biochemical analysis: The alpha1(I) and alpha2(I) chains in the medium fraction and in the cell layer show a slower migration and a broader appearance on SDS-PAGE. In the cell layer a strong and broad band migrating at the position of a pNalpha1(I) chain appears to be retained intracellularly.
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F2
Figure 2 shows the routine diagnostic SDS-PAGE gel obtained by loading 50 mul of 14C proline-labeled collagens extracted from cultured fibroblasts of the patient P and three different controls (C1, C2, and C3). On SDS-PAGE (Figure 2, medium fraction) in the patient fibroblasts (P) both alpha1(I) and alpha2(I) chains in the medium fraction as well as in the cell layer presented as overmodified bands with a slower migration and a broader appearance compared to controls (C1, C2, and C3). Furthermore, the cell layer from the patient fibroblasts (P) presented an additional broad alpha'1(I) band that migrates above the overmodified alpha1(I) band and appears to be intracellularly retained (alpha'1(I) in Figure 2, cell layer). The overmodified alpha1(I) and alpha2(I) chains detected on SDS-PAGE in the medium fraction (Figure 2) correspond to the fully processed and secreted triple-helical chains and likely result from the slower formation of the collagen triple helix as a consequence of the COL1A2 p.Gly901Ser mutation. Whereas, the overmodified and intracellularly retained alpha'1(I) band (Figure 2, cell layer) may represent those overmodified alpha1(I) chains harboring the COL1A1 c.133C>G (p.Leu45Val) variant.