Mutation m.15923A>G in the MT-TT gene causes mild myopathy - case report of an adult-onset phenotype.
Mutation m.15923A>G in the MT-TT gene causes mild myopathy - case report of an adult-onset phenotype.
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DOI：
10.1186/s12883-018-1159-4
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发表时间：
2018-09-20
期刊：
影响因子：
2.6
通讯作者：
Majamaa K
中科院分区：
文献类型：
--
作者：
Kärppä M;Kytövuori L;Saari M;Majamaa K
此前只有 5 名患者被报道存在编码线粒体 tRNA 苏氨酸的 MT-TT 基因突变。在三名受影响严重的儿童中发现了 m.15923A > G 突变。其中一名患者在出生后几天内死亡，两名患者在儿童早期患有带有参差不齐的红纤维的肌阵挛癫痫（MERRF）表型。我们现在在一名患有轻度肌病的成年患者中发现了这种突变。患者是一名64岁的芬兰男性，50多岁时出现双侧上睑下垂、复视和运动不耐受。家族史无异常。肌肉组织学显示细胞色素 c 氧化酶 (COX) 阴性且红色纤维参差不齐。 m.15923A G突变异质性在骨骼肌中为33%，在颊上皮细胞中为2%。这种突变在血液中无法检测到。进行单纤维分析后发现，COX 阴性纤维的异质性高达 92%，而正常纤维的异质性为 43%。我们报告第四例 m 患者。 15923A > G，表型比前三位患者明显温和。我们的发现和最近的生化研究表明，突变 m.15923A > G 是一种明确的致病突变。我们的结果还表明 m.15923A > G 突变的异质性与表型的严重程度相关。这项研究扩大了 mtDNA 突变引起的表型目录。
Only five patients have previously been reported to harbor mutations in the MT-TT gene encoding mitochondrial tRNA threonine. The m.15923A > G mutation has been found in three severely affected children. One of these patients died within days after birth and two had a phenotype of myoclonic epilepsy with ragged red fibers (MERRF) in early childhood. We have now found the mutation in an adult patient with mild myopathy. The patient is a 64-year-old Finnish man, who developed bilateral ptosis, diplopia and exercise intolerance in his fifties. Family history was unremarkable. Muscle histology showed cytochrome c-oxidase (COX) negative and ragged red fibres. The m.15923A > G mutation heteroplasmy was 33% in the skeletal muscle and 2% in buccal epithelial cells. The mutation was undetectable in the blood. Single-fibre analysis was performed and COX-negative fibres had a substantially higher heteroplasmy of 92%, than the normal fibres in which it was 43%. We report the fourth patient with m. 15923A > G and with a remarkably milder phenotype than the previous three patients. Our findings and recent biochemical studies suggest that the mutation m.15923A > G is a definite disease-causing mutation. Our results also suggest that heteroplasmy of the m.15923A > G mutation correlates with the severity of the phenotype. This study expands the catalog of the phenotypes caused by mutations in mtDNA.
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