Wellcome Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Wellcome Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE2 4HH, UK.
Mitochondrion. 2019 Jul;47:18-23. doi: 10.1016/j.mito.2019.04.007. Epub 2019 Apr 22.
Mitochondrial DNA variants in the MT-TM (mt-tRNA) 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.
线粒体 DNA 变体在 MT-TM（mt-tRNA）基因中很少见，通常与肌病表型相关。我们鉴定出一种新型的 MT-TM 变体，导致儿童期起病的肌病、视网膜病变、身材矮小和脑脊液乳酸升高，伴有神经影像学双侧基底节改变。肌肉活检证实存在多种呼吸链缺陷和局部细胞色素 c 氧化酶（COX）组织化学异常。线粒体基因组的下一代测序显示，在肌肉中存在一种新型的 m.4412G>A 变体，其异质性水平很高，符合致病性的所有公认标准，包括在单个肌肉纤维内的分离，从而拓宽了与线粒体 tRNA 相关疾病的基因型和表型范围。
