RT期刊文章SR电子T1协会Copresence肌萎缩性脊髓侧索硬化症和预后相关的致病变种摩根富林明神经病学神经学乔FD Lippincott Williams &威尔金斯10.1212 SP / WNL。首页0000000000207367 10.1212 / WNL。0000000000207367 A1阿德里亚诺亚蔡A1克里斯蒂娜Moglia A1安东尼奥Canosa A1 Umberto Manera A1 Maurizio Grassano A1罗萨里奥Vasta A1弗朗西斯卡帕伦博A1萨尔瓦多Gallone A1莫拉Brunetti A1马可barberi A1法比奥·德·马奇A1克利夫顿Dalgard A1露丝Chia A1 Gabriele莫拉A1芭芭拉Iazzolino A1劳拉Peotta A1布莱恩j . Traynor A1卢西亚Corrado A1桑德拉dalfonso A1莱蒂齐亚马志尼A1安德里亚·卡尔沃年2023 UL //www.ez-admanager.com/content/early/2023/05/18/WNL.0000000000207367.abstract AB的目标。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年,差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.

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