Evidence map›Paper›PMID 38816421›Full record

ArticleCell death & disease2024

Biallelic variants in CSMD1 are implicated in a neurodevelopmental disorder with intellectual disability and variable cortical malformations.

Elizabeth A Werren, Emily R Peirent, Henna Jantti, Alba Guxholli, Kinshuk Raj Srivastava, Naama Orenstein, Vinodh Narayanan, Wojciech Wiszniewski, Mateusz Dawidziuk, Pawel Gawlinski and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Genes & diseases · 2025
    Article
  7. Potential Association of theInternational journal of molecular sciences · 2025
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
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

30 authors.

Elizabeth A WerrenDepartment of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.ORCID 0000-0002-0151-2564
Emily R PeirentNeuroscience Graduate Program, University of Michigan, Ann Arbor, MI, 48109, USA.
Henna JanttiStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Alba GuxholliDepartment of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
Kinshuk Raj SrivastavaMedicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India.
Naama OrensteinSchneider Children's Medical Center of Israel, Petah Tikva, 4920235, Israel.
Vinodh NarayananCenter for Rare Childhood Disorders, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA.
Wojciech WiszniewskiDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, 97239, USA.
Mateusz DawidziukDepartment of Medical Genetics, Institute of Mother and Child, Warsaw, 01-211, Poland.
Pawel GawlinskiDepartment of Medical Genetics, Institute of Mother and Child, Warsaw, 01-211, Poland.
Muhammad UmairMedical Genomics Research Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, 11481, Saudi Arabia.
Amjad KhanDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, 97239, USA.ORCID 0000-0002-4149-9544
Shahid Niaz KhanDepartment of Zoology, Kohat University of Science and Technology, Kohat, Pakistan.
David GenevièveMontpellier University, Inserm Unit U1183, Reference Center for Rare Diseases and Developmental Anomalies, CHU, 34000, Montpellier, France.ORCID 0000-0001-6928-6287
Daphné LehalleSorbonne University, Department of Medical Genetics, Hospital Armand Trousseau, 75012, Paris, France.
K L I van GassenDepartment of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, 3584 EA, The Netherlands.
Jacques C GiltayDepartment of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, 3584 EA, The Netherlands.
Renske OegemaDepartment of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, 3584 EA, The Netherlands.ORCID 0000-0002-7146-617X
Richard H van JaarsveldDepartment of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, 3584 EA, The Netherlands.
Rafiullah RafiullahDepartment of Biotechnology, Faculty of Life Sciences, BUITEMS, Quetta, 87300, Pakistan.
Gudrun A RappoldDepartment of Human Molecular Genetics, Institute of Human Genetics, Ruprecht-Karls-University, Heidelberg, 69120, Germany.
Rachel RabinDepartment of Pediatrics, NYU Grossman School of Medicine, New York, NY, 10016, USA.
John G PappasDepartment of Pediatrics, NYU Grossman School of Medicine, New York, NY, 10016, USA.
Marsha M WheelerDepartment of Genome Sciences, University of Washington, Seattle, WA, 98195, USA.
Michael J BamshadDepartment of Pediatrics, University of Washington, Seattle, WA, 98195, USA.
Yao-Chang TsanDivision of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
Matthew B JohnsonStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Catherine E KeeganDepartment of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
Anshika Srivastava *Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India. asrivastavapgi@gmail.com.
Stephanie L Bielas *Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. sbielas@umich.edu.ORCID 0000-0003-0567-5632

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development R01 AWD010411U.S. Department of Health & Human Services | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) R01AWD010411
6 · The paper itself

Abstract

CSMD1 (Cub and Sushi Multiple Domains 1) is a well-recognized regulator of the complement cascade, an important component of the innate immune response. CSMD1 is highly expressed in the central nervous system (CNS) where emergent functions of the complement pathway modulate neural development and synaptic activity. While a genetic risk factor for neuropsychiatric disorders, the role of CSMD1 in neurodevelopmental disorders is unclear. Through international variant sharing, we identified inherited biallelic CSMD1 variants in eight individuals from six families of diverse ancestry who present with global developmental delay, intellectual disability, microcephaly, and polymicrogyria. We modeled CSMD1 loss-of-function (LOF) pathogenesis in early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells (hESCs). We show that CSMD1 is necessary for neuroepithelial cytoarchitecture and synchronous differentiation. In summary, we identified a critical role for CSMD1 in brain development and biallelic CSMD1 variants as the molecular basis of a previously undefined neurodevelopmental disorder.

Indexed as

Intellectual DisabilityMembrane ProteinsAllelesCell DifferentiationChildChild, PreschoolFemaleHumansMaleMalformations of Cortical DevelopmentNeurodevelopmental DisordersTumor Suppressor ProteinsCSMD1 protein, humanMembrane ProteinsTumor Suppressor Proteins

Identifiers

PMID38816421
PMCPMC11140003

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.