摘要：SummaryChronic kidney disease (CKD) is a major clinical sign of patients with Bardet-Biedl syndrome (BBS), especially in those carryingBBS10mutations. Twenty-nine patients with BBS and 30 controls underwent a serum-targeted metabolomic analysis.In vitrostudies were conducted in two kidney-derived epithelial cell lines, whereBbs10was stably deleted (IMCD3-Bbs10−/−cells) and over-expressed. The CKD status affected plasmatic metabolite fingerprinting in both patients with BBS and controls. Specific phosphatidylcholine and acylcarnitines discriminated eGFR decline only in patients with BBS. IMCD3-Bbs10−/ cells displayed intracellular lipidaccumulation, reduced mitochondrial potential membrane and citrate synthase staining. Mass-Spectrometry-based analysis revealed that human BBS10 interacted with six mitochondrial proteins,in vitro.In conclusion, renal dysfunction correlated with abnormal phosphatidylcholine and acylcarnitines plasma levels in patients with BBS;in vitro,Bbs10depletion caused mitochondrial defects while human BBS10 interacted with several mitochondria-related proteins, suggesting an unexplored role of this protein.Graphical abstractDisplay OmittedHighlights•Targeted Metabolomics reveals a unique serum fingerprinting of patients with BBS with CKD•Acylcarnitines are among the most significant alterations•In renal epithelial cells,Bbs10depletion leads to mitochondrial abnormalities•Human BBS 10 interacts with six mitochondria-related proteinsPathophysiology; Metabolomics
