Evidence map›Paper›PMID 34779586›Full record

ArticleEMBO molecular medicine2021

BET1 variants establish impaired vesicular transport as a cause for muscular dystrophy with epilepsy.

Sandra Donkervoort, Niklas Krause, Mykola Dergai, Pomi Yun, Judith Koliwer, Svetlana Gorokhova, Janelle Geist Hauserman, Beryl B Cummings, Ying Hu, Rosemarie Smith and 19 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% of its field
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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
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  3. The lactate sensor NDRG3 decelerates ER-to-Golgi transport through interaction with the long isoform of syntaxin-5.Proceedings of the National Academy of Sciences of the United States of America · 2025
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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

29 authors at 11 institutions in 4 countries.

Sandra DonkervoortNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-6399-1444
Niklas KrauseBiochemistry III/Faculty of Chemistry, Bielefeld University, Bielefeld, Germany.ORCID 0000-0003-1566-7281
Mykola DergaiDepartment of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
Pomi YunNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Judith KoliwerBiochemistry III/Faculty of Chemistry, Bielefeld University, Bielefeld, Germany.
Svetlana GorokhovaNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-6870-4061
Janelle Geist HausermanNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-6249-825X
Beryl B CummingsCenter for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Ying HuNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Rosemarie SmithMaine Medical Center, Portland, ME, USA.
Prech UapinyoyingNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Vijay S GaneshCenter for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Partha S GhoshDepartment of Neurology, Boston Children's Hospital, Boston, MA, USA.
Kristin G MonaghanGeneDx, Gaithersburg, MD, USA.
Seby L EdasseryDepartment of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.ORCID 0000-0003-1129-748X
Pia E FerleBiochemistry III/Faculty of Chemistry, Bielefeld University, Bielefeld, Germany.
Sarah SilversteinNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Katherine R ChaoCenter for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-2897-2410
Molly SnyderDepartment of Neurology, Children's Health, Dallas, TX, USA.
Sara EllingwoodMaine Medical Center, Portland, ME, USA.
Diana Bharucha-GoebelNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Susan T IannacconeDivision of Pediatric Neurology, Departments of Pediatrics, Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Matteo Dal PeraroInstitute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
A Reghan FoleyNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Jeffrey N SavasDepartment of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Véronique BolducNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-1690-9270
Dirk FasshauerDepartment of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.ORCID 0000-0002-1040-4282
Carsten G BönnemannNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Michael SchwakeBiochemistry III/Faculty of Chemistry, Bielefeld University, Bielefeld, Germany.ORCID 0000-0002-4173-2166
National Institutes of Health · USBielefeld University · DEBroad Institute · USNorthwestern University · USMaine Medical Center · USUniversity of Lausanne · CHBoston Children's Hospital · USÉcole Polytechnique Fédérale de Lausanne · CHRutgers, The State University of New Jersey · USStanford Health Care · USThe University of Texas Southwestern Medical Center · US

Funding

Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5M
Partners Healthcare Training Program in Precision and Genomic MedicineT32HG010464 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI HEIDI L REHM, JORDAN W SMOLLER · 2019 to 2026
$3.1M
A powerful web-based discovery platform for rare disease geneticsR01HG009141 · NHGRI · BROAD INSTITUTE, INC. · PI QUINLAN, AARON R, REHM, HEIDI L · 2017 to 2020
$2.9M
NHGRI NIH HHS R01 HG009141NHGRI NIH HHS T32 HG010464NHGRI NIH HHS UM1 HG008900
6 · The paper itself

Abstract

BET1 is required, together with its SNARE complex partners GOSR2, SEC22b, and Syntaxin-5 for fusion of endoplasmic reticulum-derived vesicles with the ER-Golgi intermediate compartment (ERGIC) and the cis-Golgi. Here, we report three individuals, from two families, with severe congenital muscular dystrophy (CMD) and biallelic variants in BET1 (P1 p.(Asp68His)/p.(Ala45Valfs*2); P2 and P3 homozygous p.(Ile51Ser)). Due to aberrant splicing and frameshifting, the variants in P1 result in low BET1 protein levels and impaired ER-to-Golgi transport. Since in silico modeling suggested that p.(Ile51Ser) interferes with binding to interaction partners other than SNARE complex subunits, we set off and identified novel BET1 interaction partners with low affinity for p.(Ile51Ser) BET1 protein compared to wild-type, among them ERGIC-53. The BET1/ERGIC-53 interaction was validated by endogenous co-immunoprecipitation with both proteins colocalizing to the ERGIC compartment. Mislocalization of ERGIC-53 was observed in P1 and P2's derived fibroblasts; while in the p.(Ile51Ser) P2 fibroblasts specifically, mutant BET1 was also mislocalized along with ERGIC-53. Thus, we establish BET1 as a novel CMD/epilepsy gene and confirm the emerging role of ER/Golgi SNAREs in CMD.

Indexed as

EpilepsyMuscular DystrophiesEndoplasmic ReticulumGolgi ApparatusHumansProtein TransportQb-SNARE ProteinsQc-SNARE ProteinsSNARE ProteinsGOSR2 protein, humanQb-SNARE ProteinsQc-SNARE ProteinsSNARE ProteinsBET1epilepsyGOSR2muscular dystrophySNARE

Identifiers

PMID34779586
PMCPMC8649873
OpenAlexW3213884056

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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.