% 0期刊文章%阿德里亚诺亚蔡%一个安东尼奥Canosa克里斯蒂娜Moglia % %一个Umberto Manera % Maurizio Grassano %罗萨里奥Vasta %一个萨尔瓦多Gallone弗朗西斯卡帕伦博% %一个Maura Brunetti %马可barberi %法比奥·德·马奇%一露丝Chia克利夫顿Dalgard % % Gabriele Mora %一个芭芭拉Iazzolino %劳拉Peotta %布莱恩j . Traynor %卢西亚拉%一个莱蒂齐亚马志尼桑德拉dalfonso % %安德里亚·卡尔沃% T协会Copresence肌萎缩性脊髓侧索硬化症和预后相关的致病变种% D R 10.1212 / WNL 2023%。0000000000207367 % J首页神经病学% P 10.1212 / WNL。0000000000207367 X %的目标。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年,差1.08 - -2.33;p < 0.001)和UNC13AC / C(2.3年,差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. %U //www.ez-admanager.com/content/neurology/early/2023/05/18/WNL.0000000000207367.full.pdf