Tzoulis C, Papingji M, Fiskestrand T, Røste L S, Bindoff L A
Department of Neurology, Haukeland University Hospital, Bergen, Norway.
Acta Neurol Scand Suppl. 2009(189):38-41. doi: 10.1111/j.1600-0404.2009.01212.x.
To investigate two patients with late onset, progressive external ophthalmoplegia (PEO) and sensory peripheral neuropathy.
MATERIALS & METHODS: The patients aged 86 and 50 years were investigated clinically including magnetic resonance imaging of the brain, electrophysiological studies and, in one, skeletal muscle biopsy. Molecular studies included sequencing of the whole coding region of the POLG1 gene and mitochondrial DNA (mtDNA) analysis for deletions and depletion.
Both patients were compound heterozygous for gene encoding the catalytic subunit of the DNA-polymerase gamma (POLG1) mutations. One had the p.737R and p.W748S mutations while the other carried the p.T251I, p.P587L and p.W748S mutations. While these mutations have been previously described, these combinations are novel. mtDNA studies in skeletal muscle showed evidence of multiple deletions and approximately 64% depletion of the mitochondrial genome.
Our findings broaden the genotypic spectrum of POLG-associated PEO and show that in addition to multiple deletions, mtDNA depletion occurs and may contribute to the pathogenesis of this disorder.
研究两名迟发性进行性眼外肌麻痹（PEO）和感觉性周围神经病患者。
对两名年龄分别为86岁和50岁的患者进行了临床检查，包括脑部磁共振成像、电生理研究，其中一名患者还进行了骨骼肌活检。分子研究包括对POLG1基因整个编码区进行测序以及对线粒体DNA（mtDNA）的缺失和耗竭情况进行分析。
两名患者均为编码DNA聚合酶γ催化亚基（POLG1）的基因复合杂合突变。一名患者有p.737R和p.W748S突变，另一名患者携带p.T251I、p.P587L和p.W748S突变。虽然这些突变此前已有报道，但这些组合是新发现的。骨骼肌的mtDNA研究显示存在多个缺失的证据，线粒体基因组约有64%的耗竭。
我们的研究结果拓宽了与POLG相关的PEO的基因型谱，表明除了多个缺失外，mtDNA耗竭也会发生，并且可能在这种疾病的发病机制中起作用。
