Journal Article

DZNE-2022-01549

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Bi-Allelic COQ4 Variants Cause Adult-Onset Ataxia-Spasticity Spectrum Disease.

Cordts, I. ; Semmler, L. ; Prasuhn, J. ; Seibt, A. ; Herebian, D. ; Navaratnarajah, T. ; Park, J. ; Deininger, N. ; Laugwitz, L. ; Göricke, S. L. ; Lingor, P.Extern* ; Brüggemann, N. ; Münchau, A. ; Synofzik, M.DZNE* ; Timmann, D. ; Mayr, J. A. ; Haack, T. B. ; Distelmaier, F. ; Deschauer, M.

2022
Wiley New York, NY

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Please use a persistent id in citations: doi:10.1002/mds.29167

Abstract: 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.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.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.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.

Keyword(s): Ataxia: genetics (MeSH) ; Cerebellar Ataxia: genetics (MeSH) ; Humans (MeSH) ; Mitochondrial Diseases (MeSH) ; Mitochondrial Proteins: genetics (MeSH) ; Muscle Spasticity (MeSH) ; Muscle Weakness (MeSH) ; Mutation: genetics (MeSH) ; Ubiquinone: deficiency (MeSH) ; Ubiquinone: genetics (MeSH) ; Ubiquinone: metabolism (MeSH) ; cerebellar ataxia ; coenzyme Q10 deficiency ; hereditary spastic paraplegia ; mitochondriopathy

Note: CC BY: https://creativecommons.org/licenses/by/4.0/

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Contributing Institute(s):

1. Parkinson Genetics (AG Gasser 1)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2022

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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