Evidence map›Paper›PMID 40200849›Full record

ArticleMovement disorders : official journal of the Movement Disorder Society2025

Repeat Expansions with Small TTTCA Insertions in MARCHF6 Cause Familial Myoclonus without Epilepsy.

Theresa Kühnel, Elsa Leitão, Renate Lunzer, Fabian Kilpert, Sabine Kaya, Claudia Del Gamba, Kelly Astudillo, Steven Frucht, Marion Simonetta-Moreau, Eric Bieth and 3 more

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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 1 paper.

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0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

13 authors.

Theresa KühnelInstitute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.ORCID https://orcid.org/0000-0003-0629-3521
Elsa LeitãoInstitute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.ORCID https://orcid.org/0000-0001-5051-9714
Renate LunzerInstitut für Humangenetik, Medizinische Universität Innsbruck, Innsbruck, Austria.
Fabian KilpertInstitute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.ORCID https://orcid.org/0000-0001-6401-2180
Sabine KayaInstitute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Claudia Del GambaDepartment of Neurology, The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, NYU Langone Health, New York, New York, USA.ORCID https://orcid.org/0000-0003-3408-7426
Kelly AstudilloDepartment of Neurology, The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, NYU Langone Health, New York, New York, USA.ORCID https://orcid.org/0000-0002-5697-0968
Steven FruchtDepartment of Neurology, The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, NYU Langone Health, New York, New York, USA.ORCID https://orcid.org/0009-0001-1166-8749
Marion Simonetta-MoreauDepartment of Neurosciences, University Hospital of Toulouse France, NeuroImaging Center, INSERM, UMR1214 Toulouse France, Paul Sabatier Toulouse 3 University, Toulouse, France.ORCID https://orcid.org/0000-0002-2278-0410
Eric BiethGénétique Médicale, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.ORCID https://orcid.org/0000-0003-3126-5493
Iris UnterbergerDepartment of Neurology, Innsbruck Medical University, Innsbruck, Austria.ORCID https://orcid.org/0000-0001-6408-5777
Giulietta Maria RiboldiDepartment of Neurology, The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, NYU Langone Health, New York, New York, USA.ORCID https://orcid.org/0000-0003-0322-5718
Christel DepienneInstitute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.ORCID https://orcid.org/0000-0002-7212-9554

Funding

Deutsche Forschungsgemeinschaft 455314768
6 · The paper itself

Abstract

backgroundFamilial adult myoclonus epilepsy (FAME) is a rare autosomal dominant disorder caused by the same intronic TTTTA/TTTCA repeat expansion in seven distinct genes. TTTTA-only expansions are benign, whereas those containing TTTCA insertions are pathogenic.

objectiveWe investigated the genetic basis of dominant cortical myoclonus without seizures in two unrelated families.

methodsRepeat-primed polymerase chain reaction (PCR), long-range PCR, and nanopore sequencing were used to detect and characterize expansions at known FAME loci.

resultsWe identified a novel repeat expansion in MARCHF6, comprising 388 to 454 elongated TTTTA repeats and 5 to 11 TTTCA repeats at the 3'-terminus, segregating with cortical myoclonus in 8 affected individuals. This configuration shows meiotic stability but low-level somatic variability in blood. We observed an inverse correlation between the number of TTTCA repeats and the age at myoclonus onset.

conclusionsThese findings indicate that as little as five TTTCA repeats combined with expanded TTTTA repeats can cause cortical myoclonus without epilepsy, highlighting the potential mechanisms underlying FAME pathophysiology. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Indexed as

DNA Repeat ExpansionEpilepsies, MyoclonicMembrane ProteinsAdultFemaleHumansMaleMiddle AgedPedigreeMembrane Proteinsepilepsyfamilial adult myoclonus epilepsy (FAME)MARCHF6myoclonusrepeat expansion

Identifiers

PMID40200849
PMCPMC12273606

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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.