biostudies-literaturePyle AEuropean Research CouncilMedical Research CouncilNational Institute for Health Research (NIHR)Wellcome Truste6https://www.ebi.ac.uk/biostudies/studies/S-EPMC4821083biostudies-literatureUnknown1(1)<h4>Objective</h4>In this study, we report 5 patients with heterogeneous phenotypes and biochemical evidence of respiratory chain (RC) deficiency; however, the molecular diagnosis is not mitochondrial disease.<h4>Methods</h4>The reported patients were identified from a cohort of 60 patients in whom RC enzyme deficiency suggested mitochondrial disease and underwent whole-exome sequencing.<h4>Results</h4>Five patients had disease-causing variants in nonmitochondrial disease genes ORAI1, CAPN3, COLQ, EXOSC8, and ANO10, which would have been missed on targeted next-generation panels or on MitoExome analysis.<h4>Conclusions</h4>Our data demonstrate that RC abnormalities may be secondary to various cellular processes, including calcium metabolism, neuromuscular transmission, and abnormal messenger RNA degradation.Neurology. GeneticsRespiratory chain deficiency in nonmitochondrial disease.PMC4821083MC_UP_1501/2NF-SI-0514-10016MC_PC_13071101876/B/13/Z309548Cuk MFeder LKratz MChinnery PFNightingale HJGriffin HAbicht ASantibanez-Koref MKarcagi VHorvath RBaric IHolinski-Feder ECzermin BDouroudis KKleinle SPyle AKirschner JfalseRespiratory chain deficiency in nonmitochondrial disease.<h4>Objective</h4>In this study, we report 5 patients with heterogeneous phenotypes and biochemical evidence of respiratory chain (RC) deficiency; however, the molecular diagnosis is not mitochondrial disease.<h4>Methods</h4>The reported patients were identified from a cohort of 60 patients in whom RC enzyme deficiency suggested mitochondrial disease and underwent whole-exome sequencing.<h4>Results</h4>Five patients had disease-causing variants in nonmitochondrial disease genes ORAI1, CAPN3, COLQ, EXOSC8, and ANO10, which would have been missed on targeted next-generation panels or on MitoExome analysis.<h4>Conclusions</h4>Our data demonstrate that RC abnormalities may be secondary to various cellular processes, including calcium metabolism, neuromuscular transmission, and abnormal messenger RNA degradation.2015-01-01T00:00:00Z2015 Jun2025-04-26T02:16:44.58Z2019-03-27T03:11:13ZS-EPMC48210832706654510.1212/NXG.0000000000000006