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Article

Leigh syndrome T8993C mitochondrial DNA mutation: Heteroplasmy and the first clinical presentation in a Vietnamese family

  • Authors:
    • Chamara Arachchighe Lahiru Weerasinghe
    • Bich‑Hong Thi Bui
    • Thu Thi Vu
    • Hong‑Loan Thi Nguyen
    • Bao‑Khanh Phung
    • Van‑Minh Nguyen
    • Van‑Anh Pham
    • Vu‑Hung Cao
    • Tuan‑Nghia Phan
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Enzyme and Protein Technology, VNU University of Science, Hanoi 100000, Vietnam, Department of Neurology, Vietnam National Children's Hospital, Hanoi 100000, Vietnam
  • Pages: 6919-6925
    |
    Published online on: March 1, 2018
       https://doi.org/10.3892/mmr.2018.8670
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Abstract

Leigh syndrome is a rare inherited, heterogeneous and progressive neurometabolic disorder that is mainly caused by specific mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). The present study reported a case of childhood Leigh syndrome with a point mutation at bp 8,993 in the mitochondrial ATPase6 gene. A 21‑month‑old male child had developed epilepsy, muscular weakness and vomiting, which was accompanied by high fever. Magnetic resonance imaging indicated typical characteristics of Leigh syndrome, including a symmetric abnormal signal in the dorsal medulla oblongata and Sylvian fissure enlargement in association with an abnormal signal in the periventricular white matter and in the putamina and caudate heads. The diagnosis was further supported with genetic tests including polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), sequencing, and quantitative PCR. The patient was found to carry a mitochondrial T8993C (m.T8993C) mutation in peripheral blood with 94.00±1.34% heteroplasmy. Eight of his relatives were also subjected to quantification of the m.T8993C mutation. The percentages of heteroplasmy in samples taken from the grandmother, mother, aunt, cousin 1, and cousin 2 were 16.33±1.67, 66.81±0.85, 71.66±3.22, 87.00±1.79, and 91.24±2.50%, respectively. The mutation was not found in samples taken from the father, the husband of the aunt, or the grandfather of the patient. The obtained data showed that the mutation was maternally inherited and accumulated through generations. Even though the heteroplasmy levels of his mother, aunt, cousin 1, and cousin 2 were relatively high (66.81‑91.24%), they remained asymptomatic, indicating that the threshold at which this mutation shows effects is high. To the best of our knowledge, this is the first report of a case of Leigh syndrome in a Vietnamese individual harboring a mtDNA mutation at the 8,993 bp site, and showing a correlation between the heteroplasmy and clinical phenotype. These findings may be useful in helping to improve the clinical diagnosis and treatment of Leigh syndrome.
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Copy and paste a formatted citation
Spandidos Publications style
Weerasinghe CA, Bui BHT, Vu TT, Nguyen HLT, Phung BK, Nguyen VM, Pham VA, Cao VH and Phan TN: Leigh syndrome T8993C mitochondrial DNA mutation: Heteroplasmy and the first clinical presentation in a Vietnamese family. Mol Med Rep 17: 6919-6925, 2018.
APA
Weerasinghe, C.A., Bui, B.T., Vu, T.T., Nguyen, H.T., Phung, B., Nguyen, V. ... Phan, T. (2018). Leigh syndrome T8993C mitochondrial DNA mutation: Heteroplasmy and the first clinical presentation in a Vietnamese family. Molecular Medicine Reports, 17, 6919-6925. https://doi.org/10.3892/mmr.2018.8670
MLA
Weerasinghe, C. A., Bui, B. T., Vu, T. T., Nguyen, H. T., Phung, B., Nguyen, V., Pham, V., Cao, V., Phan, T."Leigh syndrome T8993C mitochondrial DNA mutation: Heteroplasmy and the first clinical presentation in a Vietnamese family". Molecular Medicine Reports 17.5 (2018): 6919-6925.
Chicago
Weerasinghe, C. A., Bui, B. T., Vu, T. T., Nguyen, H. T., Phung, B., Nguyen, V., Pham, V., Cao, V., Phan, T."Leigh syndrome T8993C mitochondrial DNA mutation: Heteroplasmy and the first clinical presentation in a Vietnamese family". Molecular Medicine Reports 17, no. 5 (2018): 6919-6925. https://doi.org/10.3892/mmr.2018.8670
Copy and paste a formatted citation
x
Spandidos Publications style
Weerasinghe CA, Bui BHT, Vu TT, Nguyen HLT, Phung BK, Nguyen VM, Pham VA, Cao VH and Phan TN: Leigh syndrome T8993C mitochondrial DNA mutation: Heteroplasmy and the first clinical presentation in a Vietnamese family. Mol Med Rep 17: 6919-6925, 2018.
APA
Weerasinghe, C.A., Bui, B.T., Vu, T.T., Nguyen, H.T., Phung, B., Nguyen, V. ... Phan, T. (2018). Leigh syndrome T8993C mitochondrial DNA mutation: Heteroplasmy and the first clinical presentation in a Vietnamese family. Molecular Medicine Reports, 17, 6919-6925. https://doi.org/10.3892/mmr.2018.8670
MLA
Weerasinghe, C. A., Bui, B. T., Vu, T. T., Nguyen, H. T., Phung, B., Nguyen, V., Pham, V., Cao, V., Phan, T."Leigh syndrome T8993C mitochondrial DNA mutation: Heteroplasmy and the first clinical presentation in a Vietnamese family". Molecular Medicine Reports 17.5 (2018): 6919-6925.
Chicago
Weerasinghe, C. A., Bui, B. T., Vu, T. T., Nguyen, H. T., Phung, B., Nguyen, V., Pham, V., Cao, V., Phan, T."Leigh syndrome T8993C mitochondrial DNA mutation: Heteroplasmy and the first clinical presentation in a Vietnamese family". Molecular Medicine Reports 17, no. 5 (2018): 6919-6925. https://doi.org/10.3892/mmr.2018.8670
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