Fig. 4: Lipidomics in patient fibroblasts with the p.Arg480His/Cys FAR1 variants.

Summation of lipidomic species per major class for controls (n = 3, black diamonds), patients 1, 2, and 3, (P1 = square, P2 = circle, P3 = triangle); mean is shown and x-fold difference of the patient mean compared with that of controls if p ≤ 0.005. a Diradylphospholipid species, b monoradylphospholipid species, and c neutral lipid species (“radyl” means either a fatty acid or fatty alcohol substituent). DG diacylglycerol, DG[O] 1-alkyl-2-acylglycerol, (L)PC (lyso)phosphatidylcholine, (L)PC[O] (lyso)plasm(a/e)nylcholine, (L)PE (lyso)phosphatidylethanolamine, (L)PE[O] (lyso)plasm(a/e)nylethanolamine, TG triacylglycerol, TG[O] 1-alkyl-2,3-diacylglycerols. d LPC[O] levels 16:0–18:0 are elevated in patients with the FAR1 variants (¹⁰log-scale). e ²Log(fold-change) of the average levels of patients and controls for PC[O] and PC species with 40–44 carbon atoms in the fatty acid side chains. PC[O] species with more double bonds (containing polyunsaturated fatty acids) accumulated more in patients whereas the corresponding PC species were reduced. f Overview of the experiment to assess ether lipid and nonether lipid synthesis from exogenous C17:0-acid in control fibroblasts and patient fibroblasts with the p.Arg480His/Cys FAR1 variants. C17:0-acid can be directly incorporated in nonether lipids or converted by FAR1 to a C17:0-alcohol which in turn can be incorporated in ether lipids. g Comparison of incorporation of C17:0-acid and C17:0-alcohol in LPC(17:0) and LPC(O-17:0), respectively. C17:0-acid is incorporated in comparable amounts in LPC(17:0) in both controls and patients whereas C17:0-alcohol incorporation in LPC(O-17:0) is fourfold elevated in patients when compared with control.