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

被引：4

作者：

Sellier, C. ^{[1
]}

Corcia, P. ^{[2
,3
]}

Vourc'h, P. ^{[2
,4
]}

Dupuis, L. ^{[1
]}

机构：

[1] Univ Strasbourg, Inserm, UMR S1329, Ctr Rech Biomd Strasbourg, Strasbourg, France

[2] Univ Tours, UMR iBrain 1253, Inserm, Tours, France

[3] CHU Bretonneau, Ctr Constitut Coordinat SLA, 2 Blvd Tonnelle, F-37044 Tours 1, France

[4] CHU Tours, Serv Biochim & Biol Mol, Tours, France

来源：

REVUE NEUROLOGIQUE | 2024年 / 180卷 / 05期

关键词：

Amyotrophic lateral sclerosis; C9ORF72; Phenotype; Pathophysiology; AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; RNA FOCI; GGGGCC REPEAT; ANTISENSE TRANSCRIPTS; RAN TRANSLATION; CPG-ISLAND; PROTEINS; DISEASE; GENE;

D O I：

10.1016/j.neurol.2024.03.008

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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. # 2024 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

引用

页码：417 / 428

页数：12

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