A novel variant in COX16 causes cytochrome c oxidase deficiency, severe fatal neonatal lactic acidosis, encephalopathy, cardiomyopathy, and liver dysfunction.
COX16
OXPHOS
assembly factor
cardio-encephalopathy
mitochondrial complex IV deficiency
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
16
07
2020
revised:
26
10
2020
accepted:
02
11
2020
pubmed:
11
11
2020
medline:
1
4
2022
entrez:
10
11
2020
Statut:
ppublish
Résumé
COX16 is involved in the biogenesis of cytochrome-c-oxidase (complex IV), the terminal complex of the mitochondrial respiratory chain. 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 complementary DNA 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.
Identifiants
pubmed: 33169484
doi: 10.1002/humu.24137
pmc: PMC7898715
doi:
Substances chimiques
COX16 protein, human
0
Membrane Proteins
0
Mitochondrial Proteins
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
135-141Informations de copyright
© 2020 The Authors. Human Mutation published by Wiley Periodicals LLC.
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