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

ABSTRACT: 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 progressive neurodegenerative disease characterized by lesions in the brainstem and basal ganglia. Among the three subjects, we identified three missense variants and two frameshift variants leading to a premature stop codon. Analysis of fibroblasts from two subjects showed reduced steady-state levels of FASTKD5 protein by immunoblot, reduced translation of the cytochrome c oxidase subunit 1, impaired assembly of complex IV, and a consequent decrease in cytochrome c oxidase enzymatic activity. The e

SUBMITTER: Antonicka H 

PROVIDER: S-EPMC12256832 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature