Department of Epileptology and Life & Brain Center, University of Bonn, Bonn, Germany.
Neurology. 2010 Feb 9;74(6):507-12. doi: 10.1212/WNL.0b013e3181cef7ab.
To present 2 families with maternally inherited severe epilepsy as the main symptom of mitochondrial disease due to point mutations at position 616 in the mitochondrial tRNA(Phe) (MT-TF) gene.
Histologic stainings were performed on skeletal muscle slices from the 2 index patients. Oxidative phosphorylation activity was measured by oxygraphic and spectrophotometric methods. The patients' complete mitochondrial DNA (mtDNA) and the relevant mtDNA region in maternal relatives were sequenced.
Muscle histology showed only decreased overall COX staining, while a combined respiratory chain defect, most severely affecting complex IV, was noted in both patients' skeletal muscle. Sequencing of the mtDNA revealed in both patients a mutation at position 616 in the MT-TF gene (T>C or T>G). These mutations disrupt a base pair in the anticodon stem at a highly conserved position. They were apparently homoplasmic in both patients, and had different heteroplasmy levels in the investigated maternal relatives.
Deleterious mutations in the mitochondrial tRNA(Phe) may solely manifest with epilepsy when segregating to homoplasmy. They may be overlooked in the absence of lactate accumulation and typical mosaic mitochondrial defects in muscle.
介绍 2 个家系，其主要症状为母系遗传的严重癫痫，由于线粒体 tRNA(Phe)（MT-TF）基因 616 位的点突变导致线粒体疾病。
对 2 名指数患者的骨骼肌切片进行组织学染色。通过测氧和分光光度法测量氧化磷酸化活性。对患者的完整线粒体 DNA（mtDNA）和母系亲属的相关 mtDNA 区域进行测序。
肌肉组织学仅显示整体 COX 染色减少，而在 2 名患者的骨骼肌中均发现了复合呼吸链缺陷，最严重的是影响复合物 IV。mtDNA 测序显示，在这 2 名患者中，MT-TF 基因 616 位发生了突变（T>C 或 T>G）。这些突变破坏了高度保守位置的反密码子茎中的一个碱基对。这些突变在 2 名患者中均为纯合子，在被调查的母系亲属中具有不同的异质比例。
当线粒体 tRNA(Phe)中的有害突变纯合时，可能仅表现为癫痫。如果在肌肉中没有乳酸堆积和典型的镶嵌性线粒体缺陷，这些突变可能会被忽略。
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