Evidence map›Paper›PMID 25047197›Full record

ArticleNature communications2014

Disrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro-costo-mandibular syndrome.

Danielle C Lynch, Timothée Revil, Jeremy Schwartzentruber, Elizabeth J Bhoj, A Micheil Innes, Ryan E Lamont, Edmond G Lemire, Bernard N Chodirker, Juliet P Taylor, Elaine H Zackai and 10 more

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

Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
2.3field-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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Ultra-Conserved Poison Exons Enable Rapid and Safe Splicing Factor Gene Expression Switches: A Hypothesis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  8. Cell-Type-Specific Splicing of Transcription Regulators andThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  9. Expert consensus on classification and diagnosis of congenital orofacial cleft.Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2025
    Article
  10. Article
  11. Review
  12. Article
  13. Cell-type-specific splicing of transcription regulators andbioRxiv : the preprint server for biology · 2024
    Article
  14. Review
  15. Poison exon annotations improve the yield of clinically relevant variants in genomic diagnostic testing.Genetics in medicine : official journal of the American College of Medical Genetics · 2023
    Article
  16. Non-ubiquitous expression of core spliceosomal protein SmB/B' in chick and mouse embryos.Developmental dynamics : an official publication of the American Association of Anatomists · 2023
    Article
  17. Article
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 14 institutions in 4 countries.

Danielle C LynchDepartment of Medical Genetics, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Timothée RevilDepartment of Human Genetics, McGill University, Montréal, Quebec, Canada H3A 1B1.
Jeremy SchwartzentruberMcGill University and Génome Québec Innovation Centre, Montréal, Quebec, Canada H3A 0G1.
Elizabeth J BhojDivision of Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
A Micheil Innes1] Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada T2N 4N1 [2] Alberta Children's Hospital Research Institute for Child and Maternal Health, Calgary, Alberta, Canada T3B 6A8.
Ryan E Lamont1] Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada T2N 4N1 [2] Alberta Children's Hospital Research Institute for Child and Maternal Health, Calgary, Alberta, Canada T3B 6A8.
Edmond G LemireDivision of Medical Genetics, Department of Pediatrics, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 0W8.
Bernard N Chodirker1] Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada R3A 1S1 [2] Department of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada R3A 1S1.
Juliet P TaylorGenetic Health Service, Auckland 1142, New Zealand.
Elaine H ZackaiDivision of Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
D Ross McLeod1] Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada T2N 4N1 [2] Alberta Children's Hospital Research Institute for Child and Maternal Health, Calgary, Alberta, Canada T3B 6A8.
Edwin P Kirk1] Sydney Children's Hospital, Randwick, New South Wales 2031, Australia [2] School of Women's and Children's Health, University of New South Wales, Randwick, New South Wales 2031, Australia.
Julie Hoover-FongGreenberg Center for Skeletal Dysplasias, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
Leah FlemingNational Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Ravi SavarirayanDepartment of Pediatrics, McGill University Health Centre, Montreal, Quebec H3Z 2Z3, Canada.
Care4Rare Canada
Jacek Majewski1] Department of Human Genetics, McGill University, Montréal, Quebec, Canada H3A 1B1 [2] McGill University and Génome Québec Innovation Centre, Montréal, Quebec, Canada H3A 0G1.
Loydie A Jerome-Majewska1] Department of Human Genetics, McGill University, Montréal, Quebec, Canada H3A 1B1 [2] Department of Pediatrics, McGill University, Montreal Children's Hospital, Montreal, Quebec, Canada H3H 1P3.
Jillian S Parboosingh1] Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada T2N 4N1 [2] Alberta Children's Hospital Research Institute for Child and Maternal Health, Calgary, Alberta, Canada T3B 6A8 [3] Department of Computer Science, University of Toronto, Ontario, Canada. [4].
Francois P Bernier1] Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada T2N 4N1 [2] Alberta Children's Hospital Research Institute for Child and Maternal Health, Calgary, Alberta, Canada T3B 6A8 [3] Department of Computer Science, University of Toronto, Ontario, Canada. [4].
University of Calgary · CAUniversity of Ottawa · CAChildren's Hospital of Philadelphia · USAlberta Children's Hospital · CAAuckland District Health Board · NZJohns Hopkins University · USMcGill University · CAMcGill University and Génome Québec Innovation Centre · CAMcGill University Health Centre · CAMontreal Children's Hospital · CANational Institutes of Health · USUniversity of Manitoba · CAUniversity of Saskatchewan · CAUNSW Sydney · AU

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Elucidating the function of highly conserved regulatory sequences is a significant challenge in genomics today. Certain intragenic highly conserved elements have been associated with regulating levels of core components of the spliceosome and alternative splicing of downstream genes. Here we identify mutations in one such element, a regulatory alternative exon of SNRPB as the cause of cerebro-costo-mandibular syndrome. This exon contains a premature termination codon that triggers nonsense-mediated mRNA decay when included in the transcript. These mutations cause increased inclusion of the alternative exon and decreased overall expression of SNRPB. We provide evidence for the functional importance of this conserved intragenic element in the regulation of alternative splicing and development, and suggest that the evolution of such a regulatory mechanism has contributed to the complexity of mammalian development.

Indexed as

MutationAlternative SplicingExonsGene Expression RegulationHumansIntellectual DisabilityMicrognathismRibsRNA StabilitysnRNP Core ProteinssnRNP Core ProteinsSNRPB protein, human

Identifiers

PMID25047197
PMCPMC4109005
OpenAlexW2045162637

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.