Fig. 1

Clinical phenotype analysis of LGMDR8 patients and prediction of structural changes and instability in the TRIM32 protein caused by the 4 missense variants. (A) Summary of the onset age, AWA and CK level in known patients. (B) Patients with homozygous missense variants in the NHL domain are arranged according to two timelines: Age of onset and Age of any walking aid (AWA). Dot with 41 in (A) and (B) represents the mean value of 41 patients who are homozygotes of D487N. (C) The schematic of 4 selected missense variants location on TRIM32 protein. (D) Structure analysis and ∆∆G calculation of TRIM32 missense variants. ∆∆G is the measure of the free energy change due to an amino acid substitution. ∆∆G ≥ 1, the substitution is defined as destabilizing (E) R394H results in H-bond with E406 breakage. (F) D487N leads to a new H-bond introduction and H-bonds breakage in E489 and S470. (G) V591M causes a loss of α-helix and replaces hydrophobic valine with a hydrophilic methionine. (H) P619S causes a loss of β-sheet and replaces hydrophobic proline with a hydrophilic serine. Red box indicates their conformational difference