Wang Fan, Liu Xiangyi, He Ji, Zhang Nan, Chen Lu, Tang Lu, Fan Dongsheng
Department of Neurology, Peking University Third Hospital, Beijing, China.
Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing, China.
Front Neurol. 2022 Apr 11;13:865264. doi: 10.3389/fneur.2022.865264. eCollection 2022.
is related to amyotrophic lateral sclerosis (ALS) in patients with a family history and is thought to cause ALS-19. We screened 448 ALS patients, including 364 sporadic ALS (sALS) and 84 familial ALS (fALS) patients with variants, in a Chinese cohort. In total, 12 missense variants were identified in this study. Of these, 3 (p.Arg106His, p.Gln164Pro, and p.Val212Leu) were absent from the in-house healthy control cohort and population databases and predicted to be likely pathogenic. Genetic burden analysis did not reveal an increase in damaging variants of the gene. We considered that most of the missense variants in were not pathogenic, but certain variants, such as p.Arg106His, p.Gln164Pro, and p.Val212Leu, were likely pathogenic. The phenotype of these three patients carrying variants revealed the typical clinical manifestations of ALS without cognitive dysfunction. We concluded that likely pathogenic variants account for ~0.67% of ALS patients in China. It is necessary to interpret the relationship between the disease and variants carefully for ALS patients with gene variants.
与有家族病史的肌萎缩侧索硬化症（ALS）相关，被认为会导致ALS - 19。我们在中国队列中筛查了448例ALS患者，包括364例散发性ALS（sALS）患者和84例携带变体的家族性ALS（fALS）患者。在本研究中总共鉴定出12个错义变体。其中，3个（p.Arg106His、p.Gln164Pro和p.Val212Leu）在内部健康对照队列和人群数据库中不存在，并预测可能具有致病性。基因负担分析未显示该基因有害变体增加。我们认为该基因中的大多数错义变体不具有致病性，但某些变体，如p.Arg106His、p.Gln164Pro和p.Val212Leu，可能具有致病性。这三名携带该基因变体患者的表型显示出无认知功能障碍的典型ALS临床表现。我们得出结论，在中国，可能致病的变体约占ALS患者的0.67%。对于携带该基因变体的ALS患者，有必要仔细解读疾病与变体之间的关系。
