Titre :

Isolated parkinsonism is an atypical presentation of GRN and C9orf72 gene mutations

Auteur(s) :

Carneiro, Fábio [Auteur]
Saracino, Dario [Auteur]
Huin, Vincent [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Clot, Fabienne [Auteur]
Delorme, Cécile [Auteur]
Méneret, Aurélie [Auteur]
Thobois, Stéphane [Auteur]
Cormier, Florence [Auteur]
Corvol, Jean Christophe [Auteur]
Lenglet, Timothée [Auteur]
Vidailhet, Marie [Auteur]
Habert, Marie-Odile [Auteur]
Gabelle, Audrey [Auteur]
Beaufils, Émilie [Auteur]
Mondon, Karl [Auteur]
Tir, Mélissa [Auteur]
Andriuta, Daniela [Auteur]
Brice, Alexis [Auteur]
Deramecourt, Vincent [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Le Ber, Isabelle [Auteur]

Titre de la revue :

Parkinsonism & Related Disorders

Numéro :

80

Pagination :

73-81

Éditeur :

Elsevier

Date de publication :

2020-09-14

ISSN :

1873-5126

Mot(s)-clé(s) en anglais :

C9orf72
GRN
Parkinson's disease
Parkinsonism
FTD
FTLD
PSP
CBS
TDP-43

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Introduction A phenotype of isolated parkinsonism mimicking Idiopathic Parkinson's Disease (IPD) is a rare clinical presentation of GRN and C9orf72 mutations, the major genetic causes of frontotemporal dementia (FTD). It ...
Lire la suite >Introduction A phenotype of isolated parkinsonism mimicking Idiopathic Parkinson's Disease (IPD) is a rare clinical presentation of GRN and C9orf72 mutations, the major genetic causes of frontotemporal dementia (FTD). It still remains controversial if this association is fortuitous or not, and which clinical clues could reliably suggest a genetic FTD etiology in IPD patients. This study aims to describe the clinical characteristics of FTD mutation carriers presenting with IPD phenotype, provide neuropathological evidence of the mutation's causality, and specifically address their “red flags” according to current IPD criteria. Methods Seven GRN and C9orf72 carriers with isolated parkinsonism at onset, and three patients from the literature were included in this study. To allow better delineation of their phenotype, the presence of supportive, exclusion and “red flag” features from MDS criteria were analyzed for each case. Results Amongst the ten patients (5 GRN, 5 C9orf72), seven fulfilled probable IPD criteria during all the disease course, while behavioral/language or motoneuron dysfunctions occurred later in three. Disease duration was longer and dopa-responsiveness was more sustained in C9orf72 than in GRN carriers. Subtle motor features, cognitive/behavioral changes, family history of dementia/ALS were suggestive clues for a genetic diagnosis. Importantly, neuropathological examination in one patient revealed typical TDP-43-inclusions without alpha-synucleinopathy, thus demonstrating the causal link between FTD mutations, TDP-43-pathology and PD phenotype. Conclusion We showed that, altogether, family history of early-onset dementia/ALS, the presence of cognitive/behavioral dysfunction and subtle motor characteristics are atypical features frequently present in the parkinsonian presentations of GRN and C9orf72 mutations .Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Projet ANR :

MUSE
Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Équipe(s) de recherche :

Alzheimer et Tauopathies

Date de dépôt :

2024-01-16T02:26:28Z
2024-11-13T14:20:27Z