@article {Chio10.1212 / WNL。0000000000207367,作者={阿德里亚诺亚蔡和克里斯蒂娜•Moglia安东尼奥Canosa Umberto Manera和Maurizio Grassano罗萨里奥Vasta弗朗西斯卡帕伦博和萨尔瓦多Gallone莫拉Brunetti马可barberi和法比奥·德·马奇克利夫顿Dalgard和露丝Chia Gabriele莫拉和芭芭拉Iazzolino和劳拉Peotta和布莱恩j . Traynor和露西亚拉和桑德拉dalfonso和莱蒂齐亚马志尼和安德里亚·卡尔沃},title ={协会Copresence肌萎缩性脊髓侧索硬化症和预后相关的致病变种},elocation-id = {10.1212 / WNL。={2023}0000000000207367},年,doi = {10.1212 / WNL。出版商0000000000207367}= {Wolters Kluwer健康,公司代表美国神经病学学会},文摘={目的。首页尽管最近的进步,目前尚不清楚的各种基因/基因变异与ALS交互修改患者的表型。本研究的目的是确定相关的遗传变异co-presence ALS disease.Methods交互影响的过程。通过标识的研究人群包括1245名ALS患者皮埃蒙特注册ALS 2007年和2016年之间,没有携带SOD1 TARDBP和付家致病性变异。控制766年意大利受试者年龄,性别,和geographically-matched病例。我们认为UNC13A (rs12608932) CAMTA1 (rs2412208) SLC11A2 (rs407135)和ZNF512B (rs2275294)变异,以及ATXN2 polyQ中间重复(> = 31)和C9orf72 GGGGCC intronic (> = 30) .Results扩展。整个队列的平均生存时间是2.67年(差1.67—-5.25)。在单变量分析只有C9orf72(2.51年,差1.74 - -3.82; p=0.016), ATXN2 (1.82 years, IQR 1.08-2.33; p\<0.001) and UNC13AC/C (2.3 years, IQR 1.3-3.9; p\<0.001) significantly reduced survival. In Cox multivariable analysis, also CAMTA1 emerged to be independently related to survival (HR 1.13, 95\% c.i. 1.001-1.30, p=0.048). The co-presence of two detrimental alleles/expansions was correlated with shorter survival. In particular, the median survival of patients with CAMTA1G/G+G/T and UNC13AC/C alleles was 1.67 years (1.16-3.08) years compared to 2.75 years (1.67-5.26) of the patients not carrying these variants (p\<0.001); the survival of patients with CAMTA1G/G+G/T alleles and ATXN2>=31 intermediate polyQ repeats was 1.75 years (0.84-2.18) (p\<0.001); the survival of patients with ATXN2>=31 polyQ repeats and UNC13AC/C allele was 1.33 years (0.84-1.75) (p\<0.001); the survival of patients with C9ORF72>=30 and UNC13AC/C allele was 1.66 years (1.41-2.16). Each pair of detrimental alleles/expansions was associated to specific clinical phenotypes.Conclusions. We showed that gene variants acting as modifiers of ALS survival or phenotype can act on their own or in unison. Overall, 54\% of patients carried at least one detrimental common variant or repeat expansion, emphasizing the clinical impact of our findings. In addition, the identification of the interactive effects of modifier genes represents a crucial clue for explaining ALS clinical heterogeneity and should be considered when designing and interpreting clinical trials results.}, issn = {0028-3878}, URL = {//www.ez-admanager.com/content/early/2023/05/18/WNL.0000000000207367}, eprint = {//www.ez-admanager.com/content/early/2023/05/18/WNL.0000000000207367.full.pdf}, journal = {Neurology} }