Natural history, phenotypic spectrum, and discriminative features of multisystemic RFC1 disease
dc.contributor.buuauthor | Erer, Sevda | |
dc.contributor.department | Uludağ Üniversitesi/Tıp Fakültesi/Dahili Tıp Bilimleri/Nöroloji Anabilim Dalı. | tr_TR |
dc.contributor.researcherid | DVY-9744-2022 | tr_TR |
dc.contributor.scopusid | 25635370800 | tr_TR |
dc.date.accessioned | 2024-01-23T12:12:03Z | |
dc.date.available | 2024-01-23T12:12:03Z | |
dc.date.issued | 2021-03-02 | |
dc.description | Çalışmada 32 yazar bulunmaktadır. Bu yazarlardan sadece Bursa Uludağ Üniversitesi mensuplarının girişleri yapılmıştır. | tr_TR |
dc.description.abstract | 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 approximate to 1.3 Scale for the Assessment and Rating of Ataxia points per year (32 cross-sectional, 17 longitudinal assessments, follow-up <= 9 years [mean 3.1 years]) but also included early falls, variable nonlinear phases of MSA-C-like progression (SARA points 2.5-5.5 per year), and premature death. Treatment trials require 330 (1-year trial) and 132 (2-year trial) patients in total to detect 50% reduced progression. Conclusions RFC1 disease is frequent and occurs across continents, with CANVAS and ACC as highly diagnostic phenotypes yet as variable, overlapping clusters along a continuous multisystemic disease spectrum, including MSA-C-overlap. Our natural history data help to inform future RFC1 treatment trials. Classification of Evidence This study provides Class II evidence that RFC1 repeat expansions are associated with CANVAS and ACC. | en_US |
dc.description.sponsorship | European Union's Horizon 2020 research and innovation program by the BMBF (01GM1607) | en_US |
dc.description.sponsorship | German Research Foundation (DFG) (418081722) | en_US |
dc.description.sponsorship | Netherlands Organization for Health Research and Development | en_US |
dc.description.sponsorship | Hersenstichting | en_US |
dc.description.sponsorship | Gossweiler Foundation | en_US |
dc.description.sponsorship | uniQure | en_US |
dc.description.sponsorship | Radboud University Medical Centre | en_US |
dc.description.sponsorship | University of Tubingen (439-0-0) | en_US |
dc.description.sponsorship | UK Research & Innovation (UKRI) Medical Research Council UK (MRC) (MR/T001712/1) | en_US |
dc.description.sponsorship | Fondazione Cariplo (20191836) | en_US |
dc.description.sponsorship | European Reference Network for Rare Neurological Diseases (739510) | en_US |
dc.description.sponsorship | Suna and Inan Kirac Foundation | en_US |
dc.description.sponsorship | Koc University | en_US |
dc.description.sponsorship | German Research Foundation (DFG) (441409627) | en_US |
dc.description.sponsorship | German Research Foundation (DFG) (779257) | en_US |
dc.identifier.citation | Erer, S. (2021). "Natural history, phenotypic spectrum, and discriminative features of multisystemic RFC1 disease". Neurology, 96(9), E1369-E1382. | en_US |
dc.identifier.doi | https://doi.org/10.1212/WNL.0000000000011528 | |
dc.identifier.endpage | E1382 | tr_TR |
dc.identifier.issn | 0028-3878 | |
dc.identifier.issn | 1526-632X | |
dc.identifier.issue | 9 | tr_TR |
dc.identifier.pubmed | 33495376 | tr_TR |
dc.identifier.scopus | 2-s2.0-85101586876 | tr_TR |
dc.identifier.startpage | E1369 | tr_TR |
dc.identifier.uri | https://www.neurology.org/doi/10.1212/WNL.0000000000011528 | |
dc.identifier.uri | https://hdl.handle.net/11452/39276 | |
dc.identifier.volume | 96 | tr_TR |
dc.identifier.wos | 000657054500020 | tr_TR |
dc.indexed.pubmed | PubMed | en_US |
dc.indexed.scopus | Scopus | en_US |
dc.indexed.wos | SCIE | en_US |
dc.language.iso | en | en_US |
dc.publisher | Lippincott Williams & Wilkins | en_US |
dc.relation.collaboration | Yurt dışı | |
dc.relation.collaboration | Sanayi | |
dc.relation.journal | Neurology | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi | tr_TR |
dc.rights | info:eu-repo/semantics/closedAccess | en_US |
dc.subject | Vestibular areflexia syndrome | en_US |
dc.subject | Cerebellar-ataxia | en_US |
dc.subject | Neuropathy | en_US |
dc.subject | Cohug | en_US |
dc.subject | Diagnosis | en_US |
dc.subject | Repeat | en_US |
dc.subject | Canvas | en_US |
dc.subject.emtree | Repetitive DNA | en_US |
dc.subject.emtree | Replication factor C | en_US |
dc.subject.emtree | RFC1 protein, human | en_US |
dc.subject.emtree | Adult | en_US |
dc.subject.emtree | Aged | en_US |
dc.subject.emtree | Ataxia | en_US |
dc.subject.emtree | Bilateral vestibulopathy | en_US |
dc.subject.emtree | Cohort analysis | en_US |
dc.subject.emtree | Diagnostic imaging | en_US |
dc.subject.emtree | Disease exacerbation | en_US |
dc.subject.emtree | Europe | en_US |
dc.subject.emtree | Exome | en_US |
dc.subject.emtree | Female | en_US |
dc.subject.emtree | Genetic screening | en_US |
dc.subject.emtree | Genetics | en_US |
dc.subject.emtree | Human | en_US |
dc.subject.emtree | Male | en_US |
dc.subject.emtree | Middle aged | en_US |
dc.subject.emtree | Nuclear magnetic resonance imaging | en_US |
dc.subject.emtree | Phenotype | en_US |
dc.subject.emtree | Predictive value | en_US |
dc.subject.emtree | Shy drager syndrome | en_US |
dc.subject.emtree | Turkey (bird) | en_US |
dc.subject.emtree | Vestibular disorder | en_US |
dc.subject.mesh | Adult | en_US |
dc.subject.mesh | Aged | en_US |
dc.subject.mesh | Ataxia | en_US |
dc.subject.mesh | Bilateral vestibulopathy | en_US |
dc.subject.mesh | Cohort studies | en_US |
dc.subject.mesh | Disease progression | en_US |
dc.subject.mesh | DNA repeat expansion | en_US |
dc.subject.mesh | Europe | en_US |
dc.subject.mesh | Exome | en_US |
dc.subject.mesh | Female | en_US |
dc.subject.mesh | Genetic testing | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Magnetic resonance imaging | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | Middle aged | en_US |
dc.subject.mesh | Multiple system atrophy | en_US |
dc.subject.mesh | Phenotype | en_US |
dc.subject.mesh | Predictive value of tests | en_US |
dc.subject.mesh | Replication protein C | en_US |
dc.subject.mesh | Turkey | en_US |
dc.subject.mesh | Vestibular diseases | en_US |
dc.subject.scopus | Machado-Joseph Disease; Spinocerebellar Ataxias; Polyglutamine | en_US |
dc.subject.wos | Clinical Neurology | en_US |
dc.title | Natural history, phenotypic spectrum, and discriminative features of multisystemic RFC1 disease | en_US |
dc.type | Article | en_US |
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