Evidence map›Paper›PMID 40239008›Full record

ArticleBrain : a journal of neurology2025

Intronic FGF14 GAA repeat expansions impact progression and survival in multiple system atrophy.

Viorica Chelban, David Pellerin, Nirosen Vijiaratnam, Hamin Lee, Yen Yee Goh, Lauren Brown, Sara Sambin, Danielle Seilhean, Stephane Lehericy, Pablo Iruzubieta and 43 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Clinical, Genetic, and Imaging Characteristics of SCA27B: Insights from a Large Dutch Cohort.Movement disorders : official journal of the Movement Disorder Society · 2026
    Article
  2. Review
  3. Article
  4. GAA-FGF14 Expansions and CACNA1A Variants: Phenotypic Overlap and Diagnostic Implications.Movement disorders : official journal of the Movement Disorder Society · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

53 authors.

Viorica ChelbanNeuromuscular Disease Department, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.ORCID 0000-0002-5817-6290
David PellerinNeuromuscular Disease Department, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Nirosen VijiaratnamClinical Research Centre for Movement Disorders and Gait, Kingston Centre, Parkinson's Foundation Centre of Excellence, Monash Health, Cheltenham, VIC 3192, Australia.ORCID 0000-0002-9671-0212
Hamin LeeNeuromuscular Disease Department, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Yen Yee GohNeuromuscular Disease Department, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Lauren BrownNeuromuscular Disease Department, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Sara SambinInstitut du Cerveau-Paris BrainInstitute-ICM, Inserm, CNRS, Sorbonne Université, Paris 75651, France.ORCID 0000-0002-5027-497X
Danielle SeilheanDépartement de Neuropathologie, Institut de Neurologie, DMU Neurosciences, Groupe Hospitalier Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, Paris 75651, France.
Stephane LehericyInstitut du Cerveau-Paris BrainInstitute-ICM, Inserm, CNRS, Sorbonne Université, Paris 75651, France.
Pablo IruzubietaNeuromuscular Disease Department, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.ORCID 0000-0003-0331-6222
Rahema MohammadNeuromuscular Disease Department, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Eleanor SelfNeuromuscular Disease Department, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Annarita ScardamagliaNeuromuscular Disease Department, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Cameron LeeNeuromuscular Disease Department, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Miriama OstrozovicovaNeuromuscular Disease Department, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.ORCID 0000-0003-1519-1535
Marie-Josée DicaireDepartment of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, QC H3A 2B4, Canada.
Christine GirgesDepartment Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Emil K GustavssonGenetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London WC1N 3BG, UK.ORCID 0000-0003-0541-7537
David MurphyDepartment Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Toby CurlessDepartment Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Joshua LaßInstitute of Neurogenetics, University of Lübeck, Lübeck 23538, Germany.
Joanne TrinhInstitute of Neurogenetics, University of Lübeck, Lübeck 23538, Germany.
Timothy RittmanDepartment of Clinical Neurosciences, Cambridge University, Cambridge CB2 0SZ, UK.ORCID 0000-0003-1063-6937
James B RoweDepartment of Clinical Neurosciences, Cambridge University, Cambridge CB2 0SZ, UK.
Marios HadjivassiliouAcademic Department of Neurosciences, Sheffield Teaching Hospitals NHS Trust, Royal Hallamshire Hospital, Sheffield S10 2JF, UK.
Neil ArchibaldDepartment of Neurology, South Tees NHS Foundation Trust, Middlesbrough TS4 3BW, UK.
Matt C DanziDr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Catherine AshtonDepartment of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, QC H3A 2B4, Canada.ORCID 0000-0001-8042-6180
Virginie RothLaboratoire de Génétique, CHRU de Nancy, Nancy 54511, France.
Marion WandzelLaboratoire de Génétique, CHRU de Nancy, Nancy 54511, France.
Warren A CheungGenomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO 64108, USA.
Djordje O GvericDepartment of Brain Sciences, Imperial College London, London W12 0NN, UK.
Bart De VilNeuropathology Lab, IBB-NeuroBiobank BB190113, Born Bunge Institute, Antwerp 2610, Belgium.
Jordan FollettDepartment of Neurology, McKnight Brain Institute, University of Florida, Florida, FL 32610, USA.
P Nigel LeighDepartment of Neuroscience, Brighton and Sussex Medical School, Brighton BN1 9PX, UK.
Lukas BeichertGerman Center for Neurodegenerative Diseases (DZNE), Tübingen 72076, Germany.
Tomi PastinenService de Génétique Clinique, CHRU de Nancy, Nancy 54511, France.
Céline BonnetLaboratoire de Génétique, CHRU de Nancy, Nancy 54511, France.
Mathilde RenaudService de Génétique Clinique, CHRU de Nancy, Nancy 54511, France.
Wassilios G MeissnerService de Neurologie-Maladies Neurodégénératives, IMNc, CRMR AMS, CHU de Bordeaux, Bordeaux 33076, France.
Anne SiebenNeuropathology Lab, IBB-NeuroBiobank BB190113, Born Bunge Institute, Antwerp 2610, Belgium.
David CrosiersFaculty of Medicine and Health Sciences, Translational Neurosciences, Born-Bunge Institute, University of Antwerp, Antwerp 2610, Belgium.
Patrick CrasFaculty of Medicine and Health Sciences, Translational Neurosciences, Born-Bunge Institute, University of Antwerp, Antwerp 2610, Belgium.
Stephan ZuchnerDr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Jean-Christophe CorvolInstitut du Cerveau-Paris BrainInstitute-ICM, Inserm, CNRS, Sorbonne Université, Paris 75651, France.
Matthew J FarrerDepartment of Neurology, McKnight Brain Institute, University of Florida, Florida, FL 32610, USA.
Matthis SynofzikGerman Center for Neurodegenerative Diseases (DZNE), Tübingen 72076, Germany.ORCID 0000-0002-2280-7273
Bernard BraisDepartment of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, QC H3A 2B4, Canada.ORCID 0000-0003-1394-3561
Tom WarnerDepartment Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.ORCID 0000-0001-6195-6995
Huw R MorrisDepartment Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.ORCID 0000-0002-5473-3774
Zane JaunmuktaneDepartment Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Tom FoltynieDepartment Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.ORCID 0000-0003-0752-1813
Henry HouldenNeuromuscular Disease Department, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.ORCID 0000-0002-2866-7777

Funding

Association of British Neurologists' Academic Clinical Training Research Fellowship 565908Association of British Neurologists' Academic Clinical Training Research Fellowship ABN 540868Department of Health and Social CareElse Kröner-Fresenius-StiftungEuropean Academy of NeurologyMedical Research Council MC_UU_00030/14Medical Research Council MR/T033371/1Multiple System Atrophy CoalitionNIHR Cambridge Biomedical Research Centre NIHR203312University College London Hospitals Biomedical Research Centre
6 · The paper itself

Abstract

Partial phenotypic overlap has been suggested between multiple system atrophy and spinocerebellar ataxia 27B, the autosomal dominant ataxia caused by an intronic GAA•TTC repeat expansion in FGF14. In this study, we investigated the frequency of FGF14 GAA•TTC repeat expansion in clinically diagnosed and pathologically confirmed multiple system atrophy cases. We screened 657 multiple system atrophy cases (193 clinically diagnosed and 464 pathologically confirmed) and 1003 controls. The FGF14 repeat locus was genotyped using long-range PCR and bidirectional repeat-primed PCRs, and expansions were confirmed with targeted long-read Oxford Nanopore Technologies sequencing. We identified 19 multiple system atrophy cases carrying an FGF14 GAA≥250 expansion (2.89%, n = 19/657), a significantly higher frequency than in controls (1.40%, n = 12/1003) (P = 0.04). Long-read Oxford Nanopore Technologies sequencing confirmed repeat sizes and polymorphisms detected by PCR, with high concordance (Pearson's r = 0.99, P < 0.0001). Seven multiple system atrophy patients had a pathogenic FGF14 GAA≥300 expansion (five pathologically confirmed and two clinically diagnosed), and 12 had intermediate GAA250-299 expansion (six pathologically confirmed and six clinically diagnosed). A similar proportion of cerebellar-predominant and parkinsonism-predominant multiple system atrophy cases had FGF14 expansions. Multiple system atrophy patients carrying an FGF14 GAA≥250 expansion exhibited severe gait ataxia, autonomic dysfunction and parkinsonism, in keeping with a multiple system atrophy phenotype, with a faster progression to falls (P = 0.03) and regular wheelchair use (P = 0.02) in comparison to the multiple system atrophy cases without FGF14 GAA expansion. The length of the GAA•TTC repeat expansion lengths was inversely correlated with survival in multiple system atrophy patients (r = -0.67; P = 0.02) but not with age of onset. Therefore, screening for FGF14 GAA•TTC repeat expansion should be considered for multiple system atrophy patients with rapid loss of mobility and for complete diagnostic accuracy at inclusion in disease-modifying multiple system atrophy drug trials.

Indexed as

Fibroblast Growth FactorsMultiple System AtrophyTrinucleotide Repeat ExpansionAdultAgedDisease ProgressionDNA Repeat ExpansionFemaleGenotypeHumansIntronsMaleMiddle AgedYoung Adultfibroblast growth factor 14Fibroblast Growth FactorsFGF14 GAA ataxiamultiple system atrophyspinocerebellar ataxia 27B

Identifiers

PMID40239008
PMCPMC12404725

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.