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A Novel Pathogenic Variant in MT-CO2 Causes an Isolated Mitochondrial Complex IV Deficiency and Late-Onset Cerebellar Ataxia

Lookup NU author(s): Charlotte Zierz, Karen Baty, Sila Hopton, Gavin Falkous, Dr Andrew Schaefer, Dr Yi NgORCiD, Professor Robert Taylor



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Both nuclear and mitochondrial DNA defects can cause isolated cytochrome c oxidase (COX; complex IV) deficiency, leading to the development of the mitochondrial disease. We report a 52-year-old female patient who presented with a late-onset, progressive cerebellar ataxia, tremor and axonal neuropathy. No family history of neurological disorder was reported. Although her muscle biopsy demonstrated a significant COX deficiency, there was no clinical and electromyographical evidence of myopathy. Electrophysiological studies identified low frequency sinusoidal postural tremor at 3 Hz, corroborating the clinical finding of cerebellar dysfunction. Complete sequencing of the mitochondrial DNA genome in muscle identified a novel MT-CO2 variant, m.8163A>G predicting p.(Tyr193Cys). We present several lines of evidence, in proving the pathogenicity of this heteroplasmic mitochondrial DNA variant, as the cause of her clinical presentation. Our findings serve as an important reminder that full mitochondrial DNA analysis should be included in the diagnostic pipeline for investigating individuals with spinocerebellar ataxia

Publication metadata

Author(s): Zierz CM, Baty K, Blakely EL, Hopton S, Falkous G, Schaefer AM, Hadjivassiliou M, Sarrigiannis PG, Ng YS, Taylor RW

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Medicine

Year: 2019

Volume: 8

Issue: 6

Online publication date: 04/06/2019

Acceptance date: 30/05/2019

Date deposited: 25/07/2019

ISSN (electronic): 2077-0383

Publisher: MDPI


DOI: 10.3390/jcm8060789


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Funder referenceFunder name
203105/Z/16/ZWellcome Trust