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Cognitive impairment profile in patients with the m.3243A> G variant in mitochondrial DNA
Satu Winqvist1, Mikko Kärppä1,2,3, Jukka S Moilanen2,3,4
1Neurocenter, Oulu University Hospital, Oulu, Finland.
Background:
The m.3243A>G variant in mitochondrial DNA is associated with a wide spectrum of clinical features ranging from asymptomatic subjects to severely symptomatic patients. Cognitive involvement is one of the clinical features, but its severity and frequency are not properly known. Here we describe neuropsychological features associated with m.3243 A > G.
Methods:
We studied 45 adult patients with m.3243 A > G and 45 healthy subjects. Comprehensive neuropsychological test battery was applied. Cognitive impairment was defined, if at least five out of seven cognitive domains were impaired compared to matched controls. Major cognitive impairment was diagnosed, if the impairment was general across the domains.
Results:
Sixteen patients (36%) with m.3243 A > G were diagnosed with cognitive impairment, and six of them (13%) had a major cognitive impairment. The median age at diagnosis of cognitive impairment was 53 years (range, 25-64). The profile consisted of impaired abstract reasoning, memory problems, motor function defects and executive problems. Executive functions were affected most, and verbal memory was affected the least. Higher variant heteroplasmy and more severe global phenotype were associated with cognitive impairment, whereas age and sex were not.
Conclusion:
Cognitive impairment is found frequently in patients with m.3243 A > G, but major cognitive impairment is not common. The impairment affects all neuropsychological domains and no specific profile could be identified.
Insights
Cognitive impairment is common in patients with the m.3243A>G mitochondrial DNA variant, affecting 36% of individuals studied. Major cognitive impairment occurred in 13%, with executive functions most impacted.
Area of Science:
- Neuroscience
- Genetics
- Mitochondrial Biology
Background:
- The m.3243A>G variant in mitochondrial DNA presents a wide range of clinical symptoms.
- Cognitive impairment is a known feature, but its prevalence and severity require further investigation.
Purpose of the Study:
- To describe the neuropsychological features associated with the m.3243A>G mitochondrial DNA variant.
- To determine the frequency and profile of cognitive impairment in affected individuals.
Main Methods:
- A comprehensive neuropsychological test battery was administered to 45 adult patients with the m.3243A>G variant and 45 healthy controls.
- Cognitive impairment was defined by impairment in at least five of seven cognitive domains compared to controls.
Main Results:
- 36% of patients (16/45) were diagnosed with cognitive impairment, and 13% (6/45) had major cognitive impairment.
- Impairment was observed across all neuropsychological domains, with executive functions most affected and verbal memory least affected.
- Higher variant heteroplasmy and a more severe global phenotype correlated with cognitive impairment.
Conclusions:
- Cognitive impairment is frequent in m.3243A>G variant carriers, though major impairment is less common.
- The cognitive profile associated with this variant is broad, affecting all domains without a specific pattern.
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