Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan Province, People's Republic of China.
Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan Province, People's Republic of China.
Hum Genet. 2019 Jul;138(7):749-756. doi: 10.1007/s00439-019-02026-4. Epub 2019 May 11.
Cytochrome c oxidase 20 (COX20)/FAM36A encodes a conserved protein that is important for the assembly of COX, complex IV of the mitochondrial respiratory chain. A homozygous mutation (p.Thr52Pro) in COX20 gene has been previously described to cause muscle hypotonia and ataxia. In this study, we describe two patients from a non-consanguineous family exhibiting autosomal recessive sensory-dominant axonal neuropathy and static encephalopathy. The whole-exome sequencing analysis revealed that both patients harbored compound heterozygous mutations (p.Lys14Arg and p.Trp74Cys) of COX20 gene. The pathogenicity of the variants was further supported by morphological alternations of mitochondria observed in sural nerve and decreased COX20 protein level of peripheral blood leucocytes derived from the patients. In conclusion, COX20 might be considered as a candidate gene for the complex inherited disease. This observation broadens the clinical and genetic spectrum of COX20-related disease. However, due to the limitation of a single-family study, additional cases and studies are definitely needed to further confirm the association.
细胞色素 c 氧化酶 20（COX20）/FAM36A 编码一种保守的蛋白质，对于 COX 的组装、线粒体呼吸链复合物 IV 非常重要。先前已经描述了 COX20 基因中的纯合突变（p.Thr52Pro）可导致肌肉张力减退和共济失调。在这项研究中，我们描述了来自一个非近亲家庭的两名患者，他们表现出自体隐性感觉优势性轴索性神经病和静止性脑病。全外显子组测序分析显示，两名患者均携带 COX20 基因的复合杂合突变（p.Lys14Arg 和 p.Trp74Cys）。从患者中提取的周围血白细胞中 COX20 蛋白水平降低以及在外周神经中观察到的线粒体形态改变进一步支持了这些变体的致病性。总之，COX20 可能被认为是复杂遗传性疾病的候选基因。这一观察结果拓宽了 COX20 相关疾病的临床和遗传谱。然而，由于单个家族研究的限制，还需要更多的病例和研究来进一步证实这种关联。
