C9ORF72 hexanucleotide repeat expansion: From ALS and FTD to a broader pathogenic role?

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY Revue neurologique Pub Date : 2024-05-01 DOI:10.1016/j.neurol.2024.03.008

C. Sellier , P. Corcia , P. Vourc’h , L. Dupuis

引用次数: 0

Abstract

The major gene underlying monogenic forms of amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) is C9ORF72. The causative mutation in C9ORF72 is an abnormal hexanucleotide (G4C2) repeat expansion (HRE) located in the first intron of the gene. The aim of this review is to propose a comprehensive update on recent developments on clinical, biological and therapeutics aspects related to C9ORF72 in order to highlight the current understanding of genotype-phenotype correlations, and also on biological machinery leading to neuronal death. We will particularly focus on the broad phenotypic presentation of C9ORF72-related diseases, that goes well beyond the classical phenotypes observed in ALS and FTD patients. Last, we will comment the possible therapeutical hopes for patients carrying a C9ORF72 HRE.

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C9ORF72 六核苷酸重复扩增：从 ALS 和 FTD 到更广泛的致病作用？

单基因肌萎缩侧索硬化症（ALS）和额颞叶痴呆症（FTD）的主要致病基因是 C9ORF72。C9ORF72 的致病突变是位于该基因第一个内含子的异常六核苷酸（G4C2）重复扩增（HRE）。本综述旨在全面介绍与 C9ORF72 相关的临床、生物学和治疗学方面的最新进展，以突出当前对基因型与表型相关性的理解，以及对导致神经元死亡的生物机制的理解。我们将特别关注 C9ORF72 相关疾病的广泛表型表现，这远远超出了在 ALS 和 FTD 患者中观察到的经典表型。最后，我们将评论携带 C9ORF72 HRE 的患者可能的治疗希望。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Revue neurologique 医学-临床神经学

CiteScore

4.80

自引率

0.00%

发文量

598

审稿时长

55 days

期刊介绍： The first issue of the Revue Neurologique, featuring an original article by Jean-Martin Charcot, was published on February 28th, 1893. Six years later, the French Society of Neurology (SFN) adopted this journal as its official publication in the year of its foundation, 1899. The Revue Neurologique was published throughout the 20th century without interruption and is indexed in all international databases (including Current Contents, Pubmed, Scopus). Ten annual issues provide original peer-reviewed clinical and research articles, and review articles giving up-to-date insights in all areas of neurology. The Revue Neurologique also publishes guidelines and recommendations. The Revue Neurologique publishes original articles, brief reports, general reviews, editorials, and letters to the editor as well as correspondence concerning articles previously published in the journal in the correspondence column.