| Title: |
Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 Disease |
| Authors: |
Traschutz, Andreas; Cortese, Andrea; Reich, Selina; Dominik, Natalia; Faber, Jennifer; Jacobi, Heike; Hartmann, Annette M.; Rujescu, Dan; Montaut, Solveig; Echaniz‐laguna, Andoni; Echaniz-Laguna, Yon Andoni; Erer, Sevda; Schütz, Valerie Cornelia; Tarnutzer, Alexander A.; Sturm, Marc; Haack, Tobias B.; Vaucamps-Diedhiou, Nadège; Puccio, Hélène; Schöls, Ludger; Klockgether, Thomas; van de Warrenburg, Bart P.; Paucar, Martin; Timmann, Dagmar; Hilgers, Ralf-Dieter; Gazulla, Jose; Strupp, Michael; Moris, German; Filla, Alessandro; Houlden, Henry; Anheim, Mathieu; Infante, Jon; Basak, A. Nazli; Synofzik, Matthis |
| Contributors: |
German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE); Eberhard Karls Universität Tübingen = University of Tübingen; UCL Institute of Neurology, Queen Square London; Università degli Studi di Pavia Italia = University of Pavia Italy = Université de Pavie Italie (UNIPV); University Hospital Bonn; Heidelberg University Hospital Heidelberg; Martin-Luther-Universität Halle Wittenberg - Martin-Luther-University Halle Wittenberg (MLU); Hôpital de Hautepierre Strasbourg; Hôpitaux Universitaires de Strasbourg (HUS); Hôpital Bicêtre AP-HP, Le Kremlin-Bicêtre; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Petites Molécules de neuroprotection, neurorégénération et remyélinisation; Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM); Mécanismes Centraux et Périphériques de la Neurodégénérescence (MCPN); Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM); Universität Zürich Zürich = University of Zurich (UZH); Institute of Medical Genetics and Applied Genomics Tübingen; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC); Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Radboud University Medical Center Nijmegen (RadboudUMC); Karolinska Institutet = Karolinska Institute Stockholm; Universität Duisburg-Essen = University of Duisburg-Essen Essen; RWTH Aachen University = Rheinisch-Westfälische Technische Hochschule Aachen (RWTH Aachen); Hospital Universitario Miguel Servet; Ludwig-Maximilians University Munich (LMU); University of Naples Federico II = Università degli studi di Napoli Federico II (UNINA); Universidad de Cantabria Santander = University of Cantabria Spain = Université de Cantabrie Espagne (UC / UniCan); Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED); Instituto de Salud Carlos III Madrid (ISCIII); ANR-15-RAR3-0011,PREPARE,Preparing for therapies in autosomal recessive ataxias(2015) |
| Source: |
ISSN: 0028-3878. |
| Publisher Information: |
CCSD; American Academy of Neurology |
| Publication Year: |
2021 |
| Subject Terms: |
[SDV.BBM]Life Sciences [q-bio]/Biochemistry; Molecular Biology |
| Description: |
OBJECTIVE: To delineate the full phenotypic spectrum, discriminative features, piloting longitudinal progression data, and sample size calculations of replication factor complex subunit 1 (RFC1) repeat expansions, recently identified as causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). METHODS: Multimodal RFC1 repeat screening (PCR, Southern blot, whole-exome/genome sequencing-based approaches) combined with cross-sectional and longitudinal deep phenotyping in (1) cross-European cohort A (70 families) with >/=2 features of CANVAS or ataxia with chronic cough (ACC) and (2) Turkish cohort B (105 families) with unselected late-onset ataxia. RESULTS: Prevalence of RFC1 disease was 67% in cohort A, 14% in unselected cohort B, 68% in clinical CANVAS, and 100% in ACC. RFC1 disease was also identified in Western and Eastern Asian individuals and even by whole-exome sequencing. Visual compensation, sensory symptoms, and cough were strong positive discriminative predictors (>90%) against RFC1-negative patients. The phenotype across 70 RFC1-positive patients was mostly multisystemic (69%), including dysautonomia (62%) and bradykinesia (28%) (overlap with cerebellar-type multiple system atrophy [MSA-C]), postural instability (49%), slow vertical saccades (17%), and chorea or dystonia (11%). Ataxia progression was approximately 1.3 Scale for the Assessment and Rating of Ataxia points per year (32 cross-sectional, 17 longitudinal assessments, follow-up |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/33495376; PUBMED: 33495376; PUBMEDCENTRAL: PMC8055326 |
| DOI: |
10.1212/WNL.0000000000011528 |
| Availability: |
https://hal.science/hal-03709465; https://hal.science/hal-03709465v1/document; https://hal.science/hal-03709465v1/file/PDF%20Datastream.pdf; https://doi.org/10.1212/WNL.0000000000011528 |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.479245AC |
| Database: |
BASE |