Gagliardi Delia, Ripellino Paolo, Meneri Megi, Del Bo Roberto, Antognozzi Sara, Comi Giacomo Pietro, Gobbi Claudio, Ratti Antonia, Ticozzi Nicola, Silani Vincenzo, Ronchi Dario, Corti Stefania
Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, University of Milan, Milan, Italy.
Neurology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Front Neurol. 2023 May 17;14:1169689. doi: 10.3389/fneur.2023.1169689. eCollection 2023.
was the first gene associated with both familial and sporadic forms of amyotrophic lateral sclerosis (ALS) and is the second most mutated gene in Caucasian ALS patients. Given their high clinical and molecular heterogeneity, a detailed characterization of -ALS patients could improve knowledge about the natural history of this disease. Here, the authors aimed to provide a clinical and molecular description of a monocentric cohort of -ALS patients.
Amyotrophic lateral sclerosis (ALS) patients referring to the neurology unit of our center between 2008 and 2021 were clinically assessed and underwent molecular testing for . Segregation studies in available family members and analysis were performed to sustain the pathogenicity of the identified variants.
Among the 576 patients in our cohort, we identified 19 individuals harboring a mutation in (3.3%), including 15 (78.9%) with a familial and four (21.1%) with a sporadic form. The spinal onset of the disease was observed in all patients, and survival was extremely variable, ranging from 8 months to over 30 years. Twelve different missense variants were identified in our cohort, including one novel mutation (p.Pro67Leu).
In the present series, we provided the first description of an Italian monocentric cohort of -ALS patients, and we expanded the repertoire of mutations. Our cohort presents several remarkable features, including variable expressivity in the same family, atypical presentation (ataxia, cognitive impairment, and other extra-motor symptoms), and different modes of inheritance of a given mutation in the same family. Given the recent authorization of -directed antisense oligonucleotide for use in -ALS patients, we recommend prompt screening for mutations in novel ALS patients with familiar or sporadic presentations.
[基因名称]是首个与家族性和散发性肌萎缩侧索硬化症（ALS）均相关的基因，并且是白种人ALS患者中第二大突变基因。鉴于其高度的临床和分子异质性，对[基因名称]相关ALS患者进行详细表征有助于增进对该疾病自然史的了解。在此，作者旨在对一个单中心队列的[基因名称]相关ALS患者进行临床和分子描述。
对2008年至2021年间转诊至我们中心神经科的肌萎缩侧索硬化症（ALS）患者进行临床评估，并对[基因名称]进行分子检测。对现有家庭成员进行分离研究并进行[分析名称]分析，以支持所鉴定的[基因名称]变体的致病性。
在我们队列的576名患者中，我们鉴定出19名携带[基因名称]突变的个体（3.3%），其中15名（78.9%）为家族性，4名（21.1%）为散发性。所有患者均观察到疾病的脊髓起病，生存期差异极大，从8个月到超过30年不等。在我们的队列中鉴定出12种不同的[基因名称]错义变体，包括一种新突变（p.Pro67Leu）。
在本系列研究中，我们首次描述了一个意大利单中心队列的[基因名称]相关ALS患者，并扩展了[基因名称]突变谱。我们的队列呈现出几个显著特征，包括同一家族中的可变表达、非典型表现（共济失调、认知障碍和其他运动外症状）以及同一家族中给定突变的不同遗传模式。鉴于最近[药物名称]导向的反义寡核苷酸已被批准用于[基因名称]相关ALS患者，我们建议对具有家族性或散发性表现的新ALS患者迅速进行[基因名称]突变筛查。
