Department of Neurology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
Department of Neurology, Center for Brain, Behavior, and Metabolism, University Medical Center Schleswig-Holstein, Lübeck, Germany.
Mov Disord. 2022 Oct;37(10):2147-2153. doi: 10.1002/mds.29167. Epub 2022 Sep 1.
COQ4 codes for a mitochondrial protein required for coenzyme Q (CoQ ) biosynthesis. Autosomal recessive COQ4-associated CoQ 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 CoQ 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.
COQ4 编码一种线粒体蛋白，该蛋白是辅酶 Q（CoQ）生物合成所必需的。常染色体隐性 COQ4 相关的 CoQ 缺乏导致早发性线粒体多器官疾病。
对包含 14303 名患者的内部外显子组和基因组数据集进行筛查，以寻找 COQ4 中存在双等位基因突变的患者。对患者进行临床特征分析，并在患者来源的细胞系中进行功能研究。
在四个不同家庭的六名成年患者中发现了六种不同的 COQ4 变异，其中三种是新发现的。三名患者表现为遗传性痉挛性截瘫，两名姐妹表现出明显的小脑共济失调，一名患者兼有两者的轻度症状。对患者来源的成纤维细胞系进行的研究表明，COQ4 蛋白的含量显著降低，CoQ 浓度降低，代谢中间产物 6-脱甲氧基泛醌的水平升高。
我们报告了 COQ4 中的双等位基因突变导致成人发病的共济失调-痉挛性截瘫表型，疾病过程比之前报道的要轻得多。© 2022 作者。运动障碍协会代表国际帕金森病和运动障碍协会由 Wiley 期刊出版公司出版。
