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Leigh syndrome T8993C mitochondrial DNA mutation: Heteroplasmy and the first clinical presentation in a Vietnamese family
Molecular Medicine Reports Số 5, năm 2018 (Tập 17, trang 6919-6925)
DOI: 10.3892/mmr.2018.8670
Tài liệu thuộc danh mục: Scopus
Mol. Med. Rep.
English
Từ khóa: mitochondrial DNA; mitochondrial DNA; MT-ATP6 protein, human; proton transporting adenosine triphosphate synthase; adult; Article; ATPase6 gene; aunt; blood sampling; case report; caudate nucleus; child; clinical article; clinical feature; cousin; family; father; female; fever; gene; gene dosage; genetic screening; grandfather; grandmother; heteroplasmy; human; husband; Leigh disease; male; maternal inheritance; medulla oblongata; middle aged; mother; muscle weakness; mutational analysis; mutational load; nuclear magnetic resonance imaging; nucleotide sequence; point mutation; polymerase chain reaction; preschool child; putamen; quantitative analysis; restriction fragment length polymorphism; Sylvian fissure; Vietnamese; vomiting; white matter; Asian continental ancestry group; genetics; infant; Leigh disease; pathology; pedigree; Viet Nam; Adult; Asian Continental Ancestry Group; Child; Child, Preschool; DNA, Mitochondrial; Female; Humans; Infant; Leigh Disease; Male; Middle Aged; Mitochondrial Proton-Translocating ATPases; Pedigree; Point Mutation; Vietnam
Tóm tắt tiếng anh
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. � 2018 Spandidos Publications. All rights reserved.
