Evidence map›Paper›PMID 25342064›Full record

ArticleJournal of medical genetics2014

Whole exome sequencing in family trios reveals de novo mutations in PURA as a cause of severe neurodevelopmental delay and learning disability.

David Hunt, Richard J Leventer, Cas Simons, Ryan Taft, Kathryn J Swoboda, Mary Gawne-Cain, DDD study, Alex C Magee, Peter D Turnpenny, Diana Baralle

Open access · hybridAbstract readCase Reports
In one paragraph

Article in Journal of medical genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 2 pooled it
5.8field-weighted citation impact, top 4% 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

62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 102 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Genes · 2026
    Article
  5. Review
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  7. Article
  8. Article
  9. A Colombian Boy with a Novel de novoMolecular syndromology · 2025
    Article
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  14. InheritedNeurology. Genetics · 2024
    Article
  15. Developmental and epileptic encephalopathies.Nature reviews. Disease primers · 2024
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Movement Disorders in PURA Syndrome: A Video Case Series.Movement disorders clinical practice · 2023
    Article

2 more citing papers are in PubMed but not listed here.

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

10 authors at 7 institutions in 3 countries.

David HuntWessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.
Richard J LeventerThe Royal Children's Hospital Department of Neurology, University of Melbourne Department of Paediatrics and the Murdoch Childrens Research Institute, Melbourne, Victoria, Australia.
Cas SimonsInstitute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland, Australia.
Ryan TaftInstitute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland, Australia Departments of Integrated Systems Biology and of Pediatrics, School of Medicine and Health Sciences, George Washington University, USA Illumina, Inc., San Diego, California, USA.
Kathryn J SwobodaPediatric Motor Disorders Research Program, Department of Neurology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Mary Gawne-CainDepartment of Radiology, Southampton General Hospital, Southampton, UK.
DDD study
Alex C MageeGenetic Medicine, Belfast City Hospital, Belfast, Northern Ireland.
Peter D TurnpennyPeninsula Clinical Genetics Service, Royal Devon and Exeter Hospital (Heavitree), Exeter, UK.
Diana BaralleWessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, Hampshire, UK.
Princess Anne Hospital · GBThe University of Queensland · AUUniversity of Ulster · GBRoyal Children's Hospital · AURoyal Devon and Exeter Hospital · GBSouthampton General Hospital · GBUniversity of Utah · US

Funding

Department of HealthWellcome TrustWellcome Trust WT098051
6 · The paper itself

Abstract

backgroundDe novo mutations are emerging as an important cause of neurocognitive impairment, and whole exome sequencing of case-parent trios is a powerful way of detecting them. Here, we report the findings in four such trios.

methodsThe Deciphering Developmental Disorders study is using whole exome sequencing in family trios to investigate children with severe, sporadic, undiagnosed developmental delay. Three of our patients were ascertained from the first 1133 children to have been investigated through this large-scale study. Case 4 was a phenotypically isolated case recruited into an undiagnosed rare disorders sequencing study.

resultsProtein-altering de novo mutations in PURA were identified in four subjects. They include two different frameshifts, one inframe deletion and one missense mutation. PURA encodes Pur-α, a highly conserved multifunctional protein that has an important role in normal postnatal brain development in animal models. The associated human phenotype of de novo heterozygous mutations in this gene is variable, but moderate to severe neurodevelopmental delay and learning disability are common to all. Neonatal hypotonia, early feeding difficulties and seizures, or 'seizure-like' movements, were also common. Additionally, it is suspected that anterior pituitary dysregulation may be within the spectrum of this disorder. Psychomotor developmental outcomes appear variable between patients, and we propose a possible genotype-phenotype correlation, with disruption of Pur repeat III resulting in a more severe phenotype.

conclusionsThese findings provide definitive evidence for the role of PURA in causing a variable syndrome of neurodevelopmental delay, learning disability, neonatal hypotonia, feeding difficulties, abnormal movements and epilepsy in humans, and help clarify the role of PURA in the previously described 5q31.3 microdeletion phenotype.

Indexed as

MutationAmino Acid SequenceAmino Acid SubstitutionBrainChildChild, PreschoolDevelopmental DisabilitiesDNA-Binding ProteinsExomeFaciesFemaleGene OrderHigh-Throughput Nucleotide SequencingHumansInfantLearning DisabilitiesDNA-Binding ProteinsPURA protein, humanTranscription FactorsClinical geneticsDevelopmentalEpilepsy and seizuresNeurology

Identifiers

PMID25342064
PMCPMC4251168
OpenAlexW2153803011

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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.