Category: Pediatric Movement Disorders
Objective: To find the causes of an early onset complex movement disorder in two sisters from a non-consanguineous family, and confirm the COX20 variants responsible for such mitochondrial disorder.
Background: Cytochrome c oxidase 20 (COX20)/FAM36A encodes a mitochondrial inner membrane protein that plays a crucial role in the assembly of COX in mitochondrial respiratory chain. Only four COX20 variants have been previously reported to cause inherited neurological disorders. We found two siblings that both suffered progressive mitochondrial dysfunction symptoms including ataxia, dystonia and neuropathy at age of 4 and novel variants of COX20 were discovered through whole-exome sequencing in those patients.
Method: We carried out detailed clinical, physical and biochemical investigations for the affected individuals, as well as EMG, EEG, fundoscopy and MRI data. Muscle and nerve biopsy were performed. The expression of COX20, COX4 and OXPHOS protein was analyzed by Western blotting and the expression of COX20 mRNA was analyzed by reverse transcription PCR. Mitochondrial function of patient’s fibroblasts were analyzed by Seahorse XF Cell Mito Stress Test and enzymatic activity of Citrate Synthase and Complex I- IV.
Results: The whole-exome sequencing revealed the same compound heterozygous variants (c.41A>G and c.222G>T) of COX20 gene in two siblings. Sural nerve biopsy confirmed demyelinating neuropathy. Biochemical analyses confirmed significantly decreased COX20, protein and impaired assembly and activity of complex IV in fibroblasts and muscle tissue derived from the proband.
Conclusion: The COX20 variants we discovered in this family might be considered as a candidate gene for the complex inherited disease.Early onset complex movement disorder might has a close relationship with mitochondrial dysfunction.
To cite this abstract in AMA style:
Y.M Liu, P.Z Li, DD. Guo, H.B LV, Y.L Zhang. Mutations of COX20 affect the assembly and function of complex IV causing early onset ataxia, dystonia and neuropathy [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/mutations-of-cox20-affect-the-assembly-and-function-of-complex-iv-causing-early-onset-ataxia-dystonia-and-neuropathy/. Accessed May 9, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/mutations-of-cox20-affect-the-assembly-and-function-of-complex-iv-causing-early-onset-ataxia-dystonia-and-neuropathy/