Evidence map›Paper›PMID 39635987›Full record

ArticleMovement disorders : official journal of the Movement Disorder Society2025

The ZFHX3 GGC Repeat Expansion Underlying Spinocerebellar Ataxia Type 4 has a Common Ancestral Founder.

Zhongbo Chen, Pilar Alvarez Jerez, Claire Anderson, Martin Paucar, Jasmaine Lee, Daniel Nilsson, Hannah Macpherson, Annarita Scardamaglia, Kylie Montgomery, John Hardy and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Movement disorders : official journal of the Movement Disorder Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Frequency of ZFHX3-Mediated Spinocerebellar Ataxia 4 in a US Undiagnosed Ataxia Cohort.Movement disorders : official journal of the Movement Disorder Society · 2026
    Article
  2. Identification of GGC Repeat Expansions in ZFHX3 among Chilean Movement Disorder Patients.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

24 authors.

Zhongbo ChenDepartment of Clinical and Movement Neuroscience, Queen Square Institute of Neurology, University College London (UCL), London, UK.ORCID 0000-0001-6668-7202
Pilar Alvarez JerezDepartment of Neurodegenerative Disease, Queen Square Institute of Neurology, UCL, London, UK.
Claire AndersonDepartment of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, UCL, London, UK.
Martin PaucarDepartment of Neurology, Karolinska University Hospital, Stockholm, Sweden.
Jasmaine LeeDepartment of Neuromuscular Disease, Queen Square Institute of Neurology, UCL, London, UK.
Daniel NilssonDepartment of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Hannah MacphersonDepartment of Neurodegenerative Disease, Queen Square Institute of Neurology, UCL, London, UK.
Annarita ScardamagliaDepartment of Neuromuscular Disease, Queen Square Institute of Neurology, UCL, London, UK.
Kylie MontgomeryDepartment of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, UCL, London, UK.
John HardyDepartment of Neurodegenerative Disease, Queen Square Institute of Neurology, UCL, London, UK.
Andrew B SingletonCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Arianna TucciWilliam Harvey Research Institute, Queen Mary University of London, London, UK.
Katherine D MathewsDepartment of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
Ying-Hui FuDepartment of Neurology, University of California San Francisco, San Francisco, California, USA.
Martin EngvallDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
José Laffita-MesaDepartment of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Inger NennesmoDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Anna WedellCentre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden.
Louis J PtáčekDepartment of Neurology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
Cornelis BlauwendraatCenter for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0001-9358-8111
Emil K GustavssonDepartment of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, UCL, London, UK.ORCID 0000-0003-0541-7537
Per SvenningssonDepartment of Neurology, Karolinska University Hospital, Stockholm, Sweden.ORCID 0000-0001-6727-3802
Mina RytenDepartment of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, UCL, London, UK.
Henry HouldenDepartment of Neuromuscular Disease, Queen Square Institute of Neurology, UCL, London, UK.ORCID 0000-0002-2866-7777

Funding

Long-read DNA sequencing of Alzheimers Disease and Related Dementias casesZIAAG000538 · NIA · NATIONAL INSTITUTE ON AGING · PI COOKSON, MARK · 2020 to 2025
$39.6M
Long-read DNA sequencing of Parkinson's disease and related disordersZIAAG000542 · NIA · NATIONAL INSTITUTE ON AGING · PI BLAUWENDRAAT, CORNELIS · 2023 to 2023
$270k
Intramural NIH HHS ZIA AG000538Intramural NIH HHS ZIA AG000542Medical Research CouncilMichael J. Fox Foundation for Parkinson's ResearchNIH HHSWellcome Trust
6 · The paper itself

Abstract

backgroundThe identification of a heterozygous exonic GGC repeat expansion in ZFHX3 underlying spinocerebellar ataxia type 4 (SCA4) has solved a 25-year diagnostic conundrum. We used adaptive long-read sequencing to decipher the pathogenic expansion in the index Utah family and an unrelated family from Iowa of Swedish ancestry. Contemporaneous to our discovery, other groups identified the same repeat expansion in affected individuals from Utah, Sweden, and Germany, highlighting the current pivotal time for detection of novel repeat expansion disorders.

methodsGiven that the pathogenic repeat expansion is rare on a population level, we proposed a common ancestor across all families. Here, we employed targeted long-read sequencing through adaptive sampling, enriching for the chr16q22 region of interest.

resultsUsing phased sequencing results from individuals from Utah, Iowa, and Southern Sweden, we confirmed a common ~2000-year-old ancestral haplotype harbouring the repeat expansion.

conclusionThis study provides further insight into the genetic architecture of SCA4. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Indexed as

Spinocerebellar AtaxiasTrinucleotide Repeat ExpansionAdultFemaleHumansIowaMaleMiddle AgedPedigreeSwedenUtahataxiahaplotypelong‐read sequencingrepeat expansion disorderspinocerebellar ataxia type 4

Identifiers

PMID39635987
PMCPMC11832790

What OpenQuestion holds

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Registered trials

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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.