In:
Movement Disorders, Wiley, Vol. 37, No. 10 ( 2022-10), p. 2147-2153
Abstract:
COQ4 codes for a mitochondrial protein required for coenzyme Q 10 (CoQ 10 ) biosynthesis. Autosomal recessive COQ4 ‐associated CoQ 10 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 CoQ 10 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
Type of Medium:
Online Resource
ISSN:
0885-3185
,
1531-8257
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
2041249-6
