Li Li-Xi, Jiang Li-Ting, Pan You-Gui, Zhang Xiao-Long, Pan Li-Zhen, Nie Zhi-Yu, Chen Yu-Hui, Jin Ling-Jing
Neurotoxin Research Center of Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Neurological Department of Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
J Mol Neurosci. 2021 Dec;71(12):2462-2467. doi: 10.1007/s12031-021-01831-9. Epub 2021 Apr 1.
Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) is a rare mitochondrial disorder associated with mutations in the POLG gene, which encodes the DNA polymerase gamma catalytic subunit. A few POLG-related SANDO cases have been reported, but the genotype-phenotype correlation remains unclear. Here, we report a patient with SANDO carrying two novel missense variants (c.2543G>C, p.G848A and c.452 T>C, p.L151P) in POLG. We also reviewed previously reported cases to systematically evaluate the clinical and genetic features of POLG-related SANDO. A total of 35 distinct variants in the coding region of POLG were identified in 63 patients with SANDO. The most frequent variant was the p.A467T variant, followed by the p.W748S variant. The clinical spectrum of SANDO is heterogeneous. No clear correlation has been observed between the mutation types and clinical phenotypes. Our findings expand the mutational spectrum of POLG and contribute to clinical management and genetic counseling for POLG-related SANDO.
感觉性共济失调性神经病、构音障碍和眼肌麻痹（SANDO）是一种罕见的线粒体疾病，与编码DNA聚合酶γ催化亚基的POLG基因突变有关。已有一些与POLG相关的SANDO病例报道，但基因型与表型的相关性仍不清楚。在此，我们报告1例携带POLG基因两个新错义变异（c.2543G>C，p.G848A和c.452T>C，p.L151P）的SANDO患者。我们还回顾了既往报道的病例，以系统评估与POLG相关的SANDO的临床和遗传特征。在63例SANDO患者中，共在POLG编码区鉴定出35种不同变异。最常见的变异是p.A467T变异，其次是p.W748S变异。SANDO的临床谱具有异质性。未观察到突变类型与临床表型之间存在明确相关性。我们的发现扩展了POLG的突变谱，并有助于与POLG相关的SANDO的临床管理和遗传咨询。
