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Updated: Aug 17, 2026
An In Vitro Approach to Study Mitochondrial Dysfunction: A Cybrid Model
Published on: March 9, 2022
A juvenile case of MELAS with T3271C mitochondrial DNA mutation
Laura Stenqvist1, Anders Paetau, Leena Valanne
1Department of Neurology, Biomedicum Helsinki, Helsinki University, FIN-00290 Helsinki, Finland. laura.stenqvist@hus.fi
Abstract:
We present here a patient with muscle fatigue and poor growth since the age of 6 y. The diagnosis of a mitochondrial disease was based on the presence of ragged red fibers in the muscle biopsy and on a combined defect of mitochondrial DNA-encoded respiratory enzymes. Epilepsia partialis continua with stroke-like episodes appeared 2 mo before death at the age of 18 and prompted a search for mitochondrial DNA mutations associated with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes. Minisequencing of the patient's DNA samples revealed a heteroplasmic T3271C mutation with a 78-94% mutation load in her fibroblasts or autopsy-derived tissue samples. This is the ninth reported non-Japanese patient with T3271C mutation. Our patient shows that despite very high proportion of mutant mtDNA, the T3271C mutation can give rise to mild symptoms in childhood and to a rapid terminal phase that simulates encephalitis.
Insights
This study details a patient with mitochondrial disease caused by a T3271C mutation in mitochondrial DNA. Despite a high mutation load, symptoms were mild in childhood, progressing rapidly later in life.
Area of Science:
- Genetics
- Neurology
- Mitochondrial Biology
Background:
- Mitochondrial diseases are a group of inherited metabolic disorders.
- Mitochondrial DNA (mtDNA) mutations can lead to a range of clinical manifestations.
- Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a severe mitochondrial disorder.
Observation:
- A patient presented with muscle fatigue and poor growth from age 6.
- Muscle biopsy showed ragged red fibers and a defect in respiratory enzymes.
- The patient developed severe neurological symptoms, including epilepsia partialis continua and stroke-like episodes, before death at age 18.
Findings:
- Genetic analysis revealed a heteroplasmic T3271C mutation in mtDNA with a high mutation load (78-94%).
- This is the ninth non-Japanese patient reported with this specific mutation.
- The T3271C mutation, despite high mutant mtDNA proportion, can present with mild childhood symptoms and a rapid terminal phase.
Implications:
- This case expands the understanding of the phenotypic variability associated with the T3271C mtDNA mutation.
- It highlights the importance of genetic testing in diagnosing complex mitochondrial disorders.
- The findings suggest that high mutant mtDNA loads do not always correlate with early-onset severe disease, challenging previous assumptions.
