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Analysis of COQ2 gene in multiple system atrophy
Kotaro Ogaki, Shinsuke Fujioka, Michael G Heckman
1Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA. ross.owen@mayo.edu.
Molecular Neurodegeneration
|November 7, 2014
Summary
This study found no evidence that COQ2 gene mutations cause multiple system atrophy (MSA). However, one patient with MSA carried a COQ2 variant previously linked to CoQ10 deficiency, suggesting a potential role in disease susceptibility.
Area of Science:
- Genetics
- Neurology
- Metabolic Disorders
Background:
- Primary Coenzyme Q10 (CoQ10) deficiency is linked to loss-of-function COQ2 mutations.
- Recessive COQ2 mutations were recently identified in Japanese families with multiple system atrophy (MSA).
- Heterozygous COQ2 variants are hypothesized to increase susceptibility to sporadic MSA.
Observation:
- The study sequenced the COQ2 gene in 97 pathologically-confirmed and 58 clinically-diagnosed MSA patients in the US.
- No homozygous or compound heterozygous pathogenic COQ2 mutations were found in the MSA cohort.
- Two heterozygous COQ2 variants of unknown significance and one carrier of a known pathogenic variant (p.S146N) were identified.
Findings:
- No pathogenic COQ2 mutations were identified in the studied MSA population.
- One MSA patient was a heterozygous carrier for the p.S146N COQ2 variant, previously associated with primary CoQ10 deficiency.
- The identified heterozygous variants were not found in control subjects.
Implications:
- The p.S146N COQ2 variant, found in a heterozygous state in an MSA patient, may increase susceptibility to MSA.
- Further research is needed to clarify the role of COQ2 variations in MSA pathogenesis.
- Re-evaluating family histories of primary CoQ10 deficiency patients for MSA occurrence is warranted.
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