A Novel Variant in COX16 Causes Cytochrome c Oxidase Deficiency, Severe Fatal Neonatal Lactic Acidosis, Encephalopathy, Cardiomyopathy and Liver Dysfunction

Alexandros G.Sfakianakis shared this article with you from Inoreader A Novel Variant in COX16 Causes Cytochrome c Oxidase Deficiency, Severe Fatal Neonatal Lactic Acidosis, Encephalopathy, Cardiomyopathy and Liver Dysfunction Μέσω Human Mutation ABSTRACT COX16 is involved in the biogenesis of cytochrome‐c‐oxidase (complex IV), the terminal complex of the mitochondrial respiratory chain (RC). We present the first report of two unrelated patients with the homozygous nonsense variant c.244C>T(p.Arg82*) in COX16 with hypertrophic cardiomyopathy, encephalopathy and severe fatal lactic acidosis and isolated complex IV deficiency. The absence of COX16 protein expression leads to a complete loss of the holo‐complex IV, as detected by western blot in patient fibroblasts. Lentiviral transduction of patient fibroblasts with wild‐type COX16 cDNA rescued complex IV biosynthesis. We hypothesize that COX16 could play a role in the copper delivery route of the COX2 module as part of the complex IV assembly. Our data provide clear evidence for the pathogenicity of the COX16 variant as a cause for the observed clinical features and the isolated complex IV deficiency in these two patients and that COX16 deficiency is a cause for mitochondrial disease. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.