Lehmann Urban Diana, Motlagh Scholle Leila, Alt Kerstin, Ludolph Albert C, Rosenbohm Angela
Department of Neurology, Ulm University, 89081 Ulm, Germany.
Department of Neurology, University of Halle/S., 06120 Halle, Germany.
Diagnostics (Basel). 2020 Jan 26;10(2):68. doi: 10.3390/diagnostics10020068.
Mitochondrial dysfunction is known to play a key role in the pathophysiological pathway of neurodegenerative disorders. Nuclear-encoded proteins are involved in mtDNA replication, including DNA polymerase gamma, which is the only known replicative mtDNA polymerase, encoded by nuclear genes Polymerase gamma 1 (POLG) and Polymerase gamma 2 (POLG2). mutations are well-known as a frequent cause of mitochondrial myopathies of nuclear origin. However, only rare descriptions of mutations leading to mitochondriopathies exist. Here we describe a 68-year-old woman presenting with a 20-year history of camptocormia, mild proximal weakness, and moderate CK increase. Muscle histology showed COX-negative fibres. Genetic analysis by next generation sequencing revealed an already reported heterozygous c.1192-8_1207dup24 mutation in the gene. This is the first report on a mutation leading to camptocormia as the main clinical phenotype, extending the phenotypic spectrum of associated diseases. This underlines the broad phenotypic spectrum found in mitochondrial diseases, especially in mitochondrial disorders of nuclear origin.
已知线粒体功能障碍在神经退行性疾病的病理生理途径中起关键作用。核编码蛋白参与线粒体DNA（mtDNA）复制，包括DNA聚合酶γ，它是唯一已知的复制性mtDNA聚合酶，由核基因聚合酶γ1（POLG）和聚合酶γ2（POLG2）编码。POLG突变是核源性线粒体肌病的常见原因。然而，导致线粒体病的POLG突变仅有罕见描述。在此，我们描述一名68岁女性，有20年脊柱前凸病史、轻度近端肌无力和肌酸激酶（CK）中度升高。肌肉组织学显示细胞色素氧化酶（COX）阴性纤维。通过下一代测序进行的基因分析揭示了该基因中一个已报道的杂合c.1192 - 8_1207dup24突变。这是关于POLG突变导致脊柱前凸作为主要临床表型的首次报告，扩展了POLG相关疾病的表型谱。这突出了线粒体疾病中发现的广泛表型谱，尤其是在核源性线粒体疾病中。
