Evidence map›Paper›PMID 41282719›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Therapeutic targeting of alternative splicing caused by a lethal noncoding structural variant in X-linked dystonia parkinsonism.

Rachita Yadav, Christine A Vaine, Aloysius Domingo, Siddharth Reed, Shivangi Shah, Dadi Gao, Kathryn O'Keefe, Monica Salani, John Lemanski, Riya Bhavsar and 18 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. 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

28 authors.

Rachita YadavCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0003-2123-5223
Christine A VaineDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-2645-8223
Aloysius DomingoCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-1396-3303
Siddharth ReedCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-3266-1570
Shivangi ShahDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Dadi GaoCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-3638-8479
Kathryn O'KeefeCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Monica SalaniCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
John LemanskiCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Riya BhavsarCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Moira A McMahonIonis Pharmaceuticals, Carlsbad, CA, USA.
Michaela JacksonIonis Pharmaceuticals, Carlsbad, CA, USA.
Margo CourtneyIonis Pharmaceuticals, Carlsbad, CA, USA.
Micaela G MurcarDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Cara Fernandez-CeradoSunshine Care Foundation, 5800 Roxas City, Capiz, Philippines.
Gierold Paul A LegardaSunshine Care Foundation, 5800 Roxas City, Capiz, Philippines.
Michelle SySunshine Care Foundation, 5800 Roxas City, Capiz, Philippines.
M Salvie Velasco-AndradaSunshine Care Foundation, 5800 Roxas City, Capiz, Philippines.
Edwin L MuñozDepartment of Pathology, College of Medicine, University of the Philippines, Manila, Philippines.
Mark Angelo C AngDepartment of Pathology, College of Medicine, University of the Philippines, Manila, Philippines.
Cid Czarina E DiestaMovement Center of Makati Med Institute of Neurological, Neurosurgical and Behavioral Sciences, Makati City, Philippines.
Serkan ErdinCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0001-6587-2625
Ellen B PenneyDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Laurie OzeliusDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-7820-1684
Nutan SharmaCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-4445-7374
C Frank BennettIonis Pharmaceuticals, Carlsbad, CA, USA.ORCID 0000-0001-9887-6251
D Cristopher BraggDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-3203-6262
Michael E TalkowskiCenter for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0003-2889-0992

Funding

Broad Institute Mendelian Genomic Research CenterU01HG011755 · NHGRI · BROAD INSTITUTE, INC. · PI Anne O'Donnell-Luria, MICHAEL E TALKOWSKI · 2021 to 2026
$14.6M
Assembling the Genetic Architecture of X-linked Dystonia ParkinsonismR01NS102423 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI David Cristopher Bragg, Clotilde Lagier-Tourenne · 2017 to 2026
$5.4M
Scalable tool and comprehensive maps to interpret structural variation across the neuropsychiatric spectrumR01MH115957 · NIMH · BROAD INSTITUTE, INC. · PI TALKOWSKI, MICHAEL E · 2019 to 2025
$5.4M
Deep Learning Approaches to Decipher the Impact of Mobile Element Insertion on Alternative Splicing in Neurological DisordersR00NS118109 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI GAO, DADI · 2023 to 2025
$696k
NHGRI NIH HHS U01 HG011755NIMH NIH HHS R01 MH115957NINDS NIH HHS R00 NS118109NINDS NIH HHS R01 NS102423
6 · The paper itself

Abstract

X-linked Dystonia-Parkinsonism (XDP) is a lethal adult-onset neurodegenerative disorder that exhibits features of dystonia and parkinsonism and is exclusively associated with a causal founder haplotype that is indigenous to the Philippines and affects Filipino males. Using patient-specific fibroblasts, neural stem cells (NSC), and other neuronal models, we discovered that cryptic alternative splicing caused by a novel SINE-VNTR-Alu (SVA) mobile element insertion into intron 32 of

Identifiers

PMID41282719
PMCPMC12633100

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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.