Fig. 8

Analysis of human patients’ biopsies reveals similar defects to those observed in RyR1-Rec mice. a Representative Western blot performed on muscle homogenate from human biopsies. C1: control, 23 years, female; C2: control, 3.5 years, male; P1: CCD (Dusty core), mutations p.M2423K + p.R2441*, 43 years, male; P2: CCD (Dusty core), mutations p.T4709M + p.R1409*, 4 years, male; P3: CCD (Dusty core), mutations p.[Ile1571Val; Arg3366His; Tyr3933Cys] + p.Val788Cysfs*96, 25 years, female; P4: CCD (Dusty Core), mutations p.R2140W + p.L4828R, 9 years, female; P5: CCD (Dusty Core), mutations p.M4000del + p.Met2312Cysfs*118, 28 years, female. b Quantification of protein amount, normalized to myosin (for RyR1, CLIMP63 and Desmin) or to GAPDH (for p62). Data are presented as mean ± SEM of 10 controls samples (CTRL) and of 5 patients’ samples (patients). The value for each patient is the mean of at least 2 Western blots. The mean value for each protein in CTRL samples was set to 1. RyR1 expression level compared to controls: P1—26 ± 6%, P2—14 ± 6%, P3—20 ± 3%, P4—23 ± 3%, P5—16 ± 2%. CLIMP63 expression level compared to control: P1—130% ± 12%, P2—1372% ± 385%, P3—466% ± 92%, P4—262% ± 35%, P5—350% ± 85%). Desmin expression level compared to control: P1—47,789% ± 6097%; P2—10,052% ± 2957%; P3—36,745% ± 7150%; P4—14,951% ± 5584%; P5—11,307% ± 2858%. Student t test RyR1 p < 0.001, CLIMP63 p = 0.016, Desmin p < 0.001 c Electron microscopy pictures obtained during the course of the diagnosis, presenting multiples stacks of membranes in the disorganized core region of the biopsies of patients P2 and P5. Similar structures were identified in the muscle biopsies of the five patients. Bar 1 µm