학술논문
A novel pathogenic m.4412G>A MT-TM mitochondrial DNA variant associated with childhood-onset seizures, myopathy and bilateral basal ganglia changes.
Document Type
Article
Author
Source
Subject
*MITOCHONDRIAL DNA
*BASAL ganglia
*CEREBROSPINAL fluid
*TRABECULAR meshwork (Eye)
*CYTOCHROME oxidase
*MUSCLE diseases
*SHORT stature
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Language
ISSN
1567-7249
Abstract
Mitochondrial DNA variants in the MT-TM (mt-tRNAMet) gene are rare, typically associated with myopathic phenotypes. We identified a novel MT-TM variant resulting in prolonged seizures with childhood-onset myopathy, retinopathy, short stature and elevated CSF lactate associated with bilateral basal ganglia changes on neuroimaging. Muscle biopsy confirmed multiple respiratory chain deficiencies and focal cytochrome c oxidase (COX) histochemical abnormalities. Next-generation sequencing of the mitochondrial genome revealed a novel m.4412G>A variant at high heteroplasmy levels in muscle that fulfils all accepted criteria for pathogenicity including segregation within single muscle fibres, thus broadening the genotypic and phenotypic landscape of mitochondrial tRNA-related disease. [ABSTRACT FROM AUTHOR]