Department of Neuroscience, Ospedale Civile S. Agostino Estense, Azienda Ospedaliero Universitaria di Modena, Modena, Italy.
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Amyotroph Lateral Scler Frontotemporal Degener. 2020 May;21(3-4):296-300. doi: 10.1080/21678421.2020.1746344. Epub 2020 Apr 6.
: To date more than 180 different mutations in the SOD1 gene have been described in ALS; some of these mutations are associated to peculiar clinical features and have contributed to the understanding of disease heterogeneity. Only 5% of SOD1 mutations involve exon 3. Here we report a novel mutation c.197A > C in the exon 3 of the SOD1 gene in two apparently unrelated ALS families with early respiratory and cognitive impairment.: In the first family two brothers developed ALS in their seventies, with arm weakness followed by bulbar involvement and behavioral breakdown. An unrelated 57-year-old man presented with progressive leg weakness and mild compromised executive functions without known family history for ALS/FTD and underwent invasive ventilation in a few months. A novel missense mutation A to C at codon 197 in exon 3 causing aminoacid substitution of arginine by threonine (N66T) was found for all of them. Harmful consequences of c.197A > C mutation on SOD1 function were suggested by in silico prediction and homology with other known mutations at the same position.: Here, we report two apparently unrelated ALS families carrying a novel SOD1 mutation (N66T), supporting its pathogenic role by primary analysis, and characterized by early bulbar, respiratory, and cognitive involvement. Early cognitive impairment has been rarely described in ALS caused by SOD1 mutations, and mainly in the later phases of the disease. This report provides additional data on the SOD1 mutation spectrum and clinical presentation of ALS, widening phenotypical characterization of SOD1 ALS.
: 迄今为止，已经在 ALS 中描述了超过 180 种不同的 SOD1 基因突变；其中一些突变与特殊的临床特征相关，并有助于理解疾病异质性。只有 5%的 SOD1 突变涉及外显子 3。在这里，我们报告了两个显然无关的 ALS 家族中外显子 3 中 SOD1 基因的 c.197A > C 新突变，这些家族具有早期呼吸和认知障碍。在第一个家族中，两个兄弟在 70 多岁时发展为 ALS，手臂无力，随后出现球部受累和行为障碍。一个无关的 57 岁男子出现进行性腿部无力和轻度执行功能受损，无已知的 ALS/FTD 家族史，并在几个月内接受了侵入性通气。在所有患者中都发现了外显子 3 中密码子 197 处的新型错义突变 A 到 C，导致精氨酸被苏氨酸取代（N66T）。c.197A > C 突变对 SOD1 功能的有害后果通过计算预测和与同一位置的其他已知突变的同源性提示。: 在这里，我们报告了两个显然无关的 ALS 家族携带一种新型的 SOD1 突变（N66T），通过初步分析支持其致病性作用，并以早期球部、呼吸和认知受累为特征。由 SOD1 突变引起的 ALS 中很少描述早期认知障碍，并且主要在疾病的后期阶段。该报告提供了关于 SOD1 突变谱和 ALS 临床表现的额外数据，扩大了 SOD1 ALS 的表型特征描述。
