Department of Neurology, Affiliated Hospital of zGuizhou Medical University, Guizhou, 550004, China.
Neuro Endocrinol Lett. 2022 Dec 29;43(6):293-302.
The association between amyotrophic lateral sclerosis (ALS) and primary progressive aphasia (PPA) is rarely seen in patients. A case of ALS-PPA with a possible reticulon 2 (RTN2) mutation was reported in this study. Moreover, we systematically reviewed the previous reports of 28 ALS cases with progressive non-fluent aphasia (PNFA) and semantic dementia (SD) to identified the unique pathologic features and strong heritability of ALS-PPA. There is a different heritability among the ALS-SD, ALS-PNFA, and the ALS-unclassified PPA groups (p=0.003). Males are more prone to have ALS-PPA than females in all the three groups (p=0.028). PPA-ALS usually starts with cognitive impairment, and the onset most often involves the bulbar. In addition, chromosome 9 open reading frame 72(C9ORF72) and TANK-binding kinase 1 (TBK1) are important pathogenic genes of PPA-ALS. Overall, heritability is of high certainty in ALS-SD, ALS-PNFA, and the ALS-unclassified PPA groups. TAR (Trans-Activator Regulatory) DNA-binding Protein 43 (TDP43) is a 100% predictive pathologic protein of ALS-PPA. C9ORF72 and TBK1 are important pathogenic genes of PPA-ALS.
肌萎缩侧索硬化症（ALS）与原发性进行性失语症（PPA）在患者中很少同时发生。本研究报道了一例可能与 RTN2 突变相关的 ALS-PPA 病例。此外，我们系统地回顾了 28 例具有进行性非流利性失语症（PNFA）和语义性痴呆（SD）的 ALS 病例的既往报告，以确定 ALS-PPA 的独特病理特征和强遗传性。ALS-SD、ALS-PNFA 和未分类的 ALS-PPA 组之间的遗传率存在差异（p=0.003）。在所有三组中，男性比女性更容易患有 ALS-PPA（p=0.028）。PPA-ALS 通常以认知障碍为首发症状，且首发部位通常累及球部。此外，染色体 9 开放阅读框 72（C9ORF72）和 TANK 结合激酶 1（TBK1）是 PPA-ALS 的重要致病基因。总体而言，ALS-SD、ALS-PNFA 和未分类的 ALS-PPA 组的遗传率具有高度确定性。TAR（Trans-Activator Regulatory）DNA 结合蛋白 43（TDP43）是 ALS-PPA 的 100%预测性病理蛋白。C9ORF72 和 TBK1 是 PPA-ALS 的重要致病基因。
