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

被引:11
|
作者
Zierz, Charlotte M. [1 ]
Baty, Karen [1 ,2 ]
Blakely, Emma L. [1 ,2 ]
Hopton, Sila [1 ,2 ]
Falkous, Gavin [1 ,2 ]
Schaefer, Andrew M. [1 ,3 ]
Hadjivassiliou, Marios [4 ]
Sarrigiannis, Ptolemaios G. [4 ,5 ]
Ng, Yi Shiau [1 ,3 ]
Taylor, Robert W. [1 ,2 ]
机构
[1] Newcastle Univ, Wellcome Ctr Mitochondrial Res, Inst Neurosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
[2] Newcastle Tyne Hosp NHS Fdn Trust, NHS Highly Specialised Mitochondrial Diagnost Lab, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
[3] Newcastle Tyne Hosp NHS Fdn Trust, Royal Victoria Infirm, Dept Neurol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England
[4] Sheffield Teaching Hosp NHS Fdn Trust, Royal Hallamshire Hosp, Acad Directorate Neurosci, Sheffield S10 2JF, S Yorkshire, England
[5] Sheffield Teaching Hosp NHS Fdn Trust, Royal Hallamshire Hosp, Dept Clin Neurophysiol, Sheffield S10 2JF, S Yorkshire, England
基金
英国生物技术与生命科学研究理事会; 英国医学研究理事会;
关键词
isolated COX deficiency; cerebellar ataxia; mitochondrial DNA; single fibre segregation studies; heteroplasmy; CYTOCHROME-C-OXIDASE; SUBUNIT-II; CONSENSUS STATEMENT; MUTATION; DIAGNOSIS; DISEASE; ALGORITHM; CODON; ASSAY; GENE;
D O I
10.3390/jcm8060789
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页数:9
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