Davidzon Guido, Greene Paul, Mancuso Michelangelo, Klos Kevin J, Ahlskog J Eric, Hirano Michio, DiMauro Salvatore
Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
Ann Neurol. 2006 May;59(5):859-62. doi: 10.1002/ana.20831.
To define the molecular etiology of early-onset parkinsonism and peripheral neuropathy.
Two sisters had early-onset parkinsonism (dystonic toe curling, action tremor, masked face, bradykinesia, stooped posture, and rigidity), together with clinical and electrophysiological signs of sensorimotor axonal peripheral neuropathy.
No mutations were found in the genes for parkin or PINK1. Muscle biopsies showed ragged-red and cytochrome c oxidase-negative fibers, and biochemistry showed decreased activities of respiratory chain complexes containing mitochondrial DNA-encoded subunits. Multiple mitochondrial DNA deletions were seen by long polymerase chain reaction, and sequencing of the POLG gene showed that the patients were compound heterozygous for two patogenic mutations.
POLG mutations can cause early-onset parkinsonism in the absence of progressive external ophthalmoplegia.
明确早发性帕金森病和周围神经病变的分子病因。
两姐妹患有早发性帕金森病（趾肌张力障碍性卷曲、动作性震颤、面具脸、运动迟缓、弯腰姿势和强直），同时伴有感觉运动轴索性周围神经病变的临床和电生理体征。
在帕金森病蛋白或PTEN诱导激酶1基因中未发现突变。肌肉活检显示有破碎红纤维和细胞色素c氧化酶阴性纤维，生化检查显示含有线粒体DNA编码亚基的呼吸链复合物活性降低。通过长链聚合酶链反应可见多个线粒体DNA缺失，POLG基因测序显示患者为两个致病突变的复合杂合子。
POLG突变可在无进行性眼外肌麻痹的情况下导致早发性帕金森病。
