Biallelic variants in COX18 cause a mitochondrial disorder primarily manifesting as peripheral neuropathy.

ABSTRACT: Defects in mitochondrial dynamics are a common cause of Charcot-Marie-Tooth disease (CMT), whereas primary deficiencies in the mitochondrial respiratory chain (MRC) are rare and atypical for this aetiology. This study aims to report COX18 as a novel CMT-causing gene. This gene encodes an assembly factor of mitochondrial Complex IV that translocates the C-terminal tail of MTCO2 across the mitochondrial inner membrane. Exome sequencing was performed in four affected individuals from three families. The patients and available family members underwent thorough neurological and electrophysiological assessment. The impact of one of the identified variants on splicing, protein levels and mitochondrial bioenergetics was investigated in patient-derived lymphoblasts. The functionality of the mutant

SUBMITTER: Armirola-Ricaurte C 

PROVIDER: S-EPMC12782158 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature