Evidence map›Paper›PMID 42236257›Full record

ArticleMovement disorders : official journal of the Movement Disorder Society2026

Frequency of ZFHX3-Mediated Spinocerebellar Ataxia 4 in a US Undiagnosed Ataxia Cohort.

Annie Chen, Udbhav Avadhani, Kathie Ngo, Rosario I Corona, George de V Carvalho Neto, Karla P Figueroa, Undiagnosed Diseases Network, Susan Perlman, Stefan M Pulst, Stanley F Nelson and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Movement disorders : official journal of the Movement Disorder Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Annie ChenDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Udbhav AvadhaniDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Kathie NgoDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Rosario I CoronaDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
George de V Carvalho NetoDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Karla P FigueroaDepartment of Neurology, University of Utah, Salt Lake City, Utah, USA.
Undiagnosed Diseases Network
Susan PerlmanDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Stefan M PulstDepartment of Neurology, University of Utah, Salt Lake City, Utah, USA.
Stanley F NelsonDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Darice WongDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Brent L FogelDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Ataxin-2 complex proteins in neurodegeneration.R35NS127253 · NINDS · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Stefan M. PULST · 2022 to 2026
$4.6M
Generous donors to the University of California.NCATS NIH HHS UL1 TR001881NCATS NIH HHS UL1TR001881NIH HHS X01NS141718NINDS NIH HHS R35 NS127253NINDS NIH HHS R35NS127253The Rindlisbacher Endowment for Neurodegeneration Research.The UCLA California Center for Rare Diseases
6 · The paper itself

Abstract

backgroundSpinocerebellar ataxia 4 (SCA4) is a late-onset dominant ataxia with neuropathy caused by exonic GGC repeat expansion in the ZFHX3 gene thought to originate from a Swedish founder event. The GC-rich expansion is highly thermodynamically stable, posing challenges for standard clinical genetic testing methods. Development of a high-throughput relatively inexpensive detection method would benefit both clinical diagnostic testing and large-scale research applications.

objectiveUsing a cost-effective high-throughput polymerase chain reaction (PCR) assay, we assessed the frequency of SCA4 repeat expansion in an undiagnosed US ataxia cohort.

methodPrimers flanking the ZFHX3 repeat region were used under optimized PCR conditions to assess for expanded GGC repeats in 687 undiagnosed ataxia patients. Repeat size was determined by fragment analysis and orthogonally confirmed with long-read sequencing (Oxford Nanopore Technologies).

resultsWe identified pathogenic SCA4 expansions in three families with cerebellar ataxia and sensory/autonomic neuropathy. The pathogenic alleles were confirmed to be of Swedish ancestry using comprehensive haplotype analysis of 14 single nucleotide polymorphisms (SNPs) previously associated with ZFHX3 expansion. Two families carried all 14 SNPs, suggesting this may represent an ancestral haplotype. Utilizing a minimal haplotype present in all reported patients, we bioinformatically assessed 852 additional subjects, for a total of 1539 screened, but did not identify additional SCA4 patients.

conclusionUsing a high-throughput cost-effective PCR assay, we identified three SCA4 families in a large US ataxia cohort. Haplotype analysis supports a common Swedish founder allele, consistent with previously reported SCA4 cases. SCA4 diagnostic testing is recommended for all patients of Swedish ancestry with undiagnosed ataxia. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Indexed as

Homeodomain ProteinsSpinocerebellar AtaxiasAdultAgedCohort StudiesDNA Repeat ExpansionFemaleHaplotypesHumansMaleMiddle AgedPolymerase Chain ReactionPolymorphism, Single NucleotideUnited StatesHomeodomain ProteinsDNA Repeat ExpansionGenetic ScreeningHaplotypesPCRSpinocerebellar Ataxia 4

Identifiers

PMID42236257
PMCPMC13602291

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.