Bi-Allelic COQ4 Variants Cause Adult-Onset Ataxia-Spasticity Spectrum Disease.
Mov Disord
; 37(10): 2147-2153, 2022 10.
Article
em En
| MEDLINE
| ID: mdl-36047608
ABSTRACT
BACKGROUND:
COQ4 codes for a mitochondrial protein required for coenzyme Q10 (CoQ10 ) biosynthesis. Autosomal recessive COQ4-associated CoQ10 deficiency leads to an early-onset mitochondrial multi-organ disorder.METHODS:
In-house exome and genome datasets (n = 14,303) were screened for patients with bi-allelic variants in COQ4. Work-up included clinical characterization and functional studies in patient-derived cell lines.RESULTS:
Six different COQ4 variants, three of them novel, were identified in six adult patients from four different families. Three patients had a phenotype of hereditary spastic paraparesis, two sisters showed a predominant cerebellar ataxia, and one patient had mild signs of both. Studies in patient-derived fibroblast lines revealed significantly reduced amounts of COQ4 protein, decreased CoQ10 concentrations, and elevated levels of the metabolic intermediate 6-demethoxyubiquinone.CONCLUSION:
We report bi-allelic variants in COQ4 causing an adult-onset ataxia-spasticity spectrum phenotype and a disease course much milder than previously reported. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Ataxia Cerebelar
/
Ubiquinona
/
Proteínas Mitocondriais
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article