Bi-allelic mutations in FASTKD5 are associated with cytochrome c oxidase deficiency and early- to late-onset Leigh syndrome

• Published in: American journal of human genetics Vol. 112; no. 7; pp. 1699 - 1710
• Main Authors: Antonicka, Hana, Weraarpachai, Woranontee, Szigety, Katherine M., Kopajtich, Robert, Gibson, James B., Van Hove, Johan L.K., Friederich, Marisa W., Lopriore, Piervito, Neuhofer, Christiane, Van Hove, Roxanne A., Cole, Michel A., Reisdorph, Richard, Peterson, James T., Dempsey, Katherine J., Ganetzky, Rebecca D., Mancuso, Michelangelo, Prokisch, Holger, Shoubridge, Eric A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.07.2025
• Subjects: Adult; Age of Onset; Alleles; cytochrome c oxidase deficiency; Cytochrome-c Oxidase Deficiency - genetics; Electron Transport Complex IV - genetics; Electron Transport Complex IV - metabolism; FASTKD5; Female; Fibroblasts - metabolism; Humans; Leigh Disease - genetics; Leigh syndrome; Male; Mitochondria; mitochondrial disease; mitochondrial DNA; mitochondrial gene expression; Mitochondrial Proteins - genetics; mitochondrial translation; Mutation - genetics; Mutation, Missense; neurodegenerative disease; RNA processing; mitochondrial translation; Leigh syndrome; neurodegenerative disease; mitochondrial gene expression; mitochondrial DNA; FASTKD5; cytochrome c oxidase deficiency; RNA processing; mitochondrial disease

Using exome sequencing, we identified compound heterozygous variants of unknown significance in FASTKD5, a gene that codes for a mitochondrial protein essential for processing mRNAs at non-canonical cleavage sites in the primary mitochondrial transcript, in three subjects with Leigh syndrome, a prog...