Evidence map›Paper›PMID 26318253›Full record

ArticleMolecular genetics and metabolism2015

Asparagine Synthetase Deficiency causes reduced proliferation of cells under conditions of limited asparagine.

Elizabeth Emma Palmer, Jaclyn Hayner, Rani Sachdev, Michael Cardamone, Tejaswi Kandula, Paula Morris, Kerith-Rae Dias, Jiang Tao, David Miller, Ying Zhu and 8 more

Open access · greenAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular genetics and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

28 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
  2. A missense variant in Exon 9 of theFrontiers in genetics · 2026
    Article
  3. Aspartate in the Brain: A Review.Neurochemical research · 2025
    Review
  4. Review
  5. Amino acid metabolism in health and disease.Signal transduction and targeted therapy · 2023
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Clinical, molecular, and biochemical delineation of asparagine synthetase deficiency in Saudi cohort.Genetics in medicine : official journal of the American College of Medical Genetics · 2020
    Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
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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

18 authors at 5 institutions in 2 countries.

Elizabeth Emma PalmerSydney Children's Hospital, High Street Randwick NSW 2031, Australia; University of New South Wales, High Street, Sydney, NSW 2052, Australia; Genetics of Learning Disability (GOLD) service, Corner of Turton and Tinonee Roads, Waratah NSW 2298.
Jaclyn HaynerDepartment of Biochemistry & Molecular Biology, University of Florida College of Medicine, 1200 Newell Drive, Florida, USA, 32608.
Rani SachdevSydney Children's Hospital, High Street Randwick NSW 2031, Australia; University of New South Wales, High Street, Sydney, NSW 2052, Australia.
Michael CardamoneSydney Children's Hospital, High Street Randwick NSW 2031, Australia; University of New South Wales, High Street, Sydney, NSW 2052, Australia.
Tejaswi KandulaSydney Children's Hospital, High Street Randwick NSW 2031, Australia; University of New South Wales, High Street, Sydney, NSW 2052, Australia.
Paula MorrisKinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
Kerith-Rae DiasKinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
Jiang TaoKinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
David MillerKinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
Ying ZhuGenetics of Learning Disability (GOLD) service, Corner of Turton and Tinonee Roads, Waratah NSW 2298.
Rebecca MacintoshSydney Children's Hospital, High Street Randwick NSW 2031, Australia.
Marcel E DingerKinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, 390 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
Mark J CowleyKinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, 390 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
Michael F BuckleyUniversity of New South Wales, High Street, Sydney, NSW 2052, Australia; Seals Molecular Genetics, POW Hospital Campus, Barker Street, Randwick, Sydney, NSW 2031, Australia.
Tony RoscioliSydney Children's Hospital, High Street Randwick NSW 2031, Australia; University of New South Wales, High Street, Sydney, NSW 2052, Australia; Seals Molecular Genetics, POW Hospital Campus, Barker Street, Randwick, Sydney, NSW 2031, Australia.
Ann ByeSydney Children's Hospital, High Street Randwick NSW 2031, Australia; University of New South Wales, High Street, Sydney, NSW 2052, Australia.
Michael S KilbergDepartment of Biochemistry & Molecular Biology, University of Florida College of Medicine, 1200 Newell Drive, Florida, USA, 32608.
Edwin P KirkSydney Children's Hospital, High Street Randwick NSW 2031, Australia; University of New South Wales, High Street, Sydney, NSW 2052, Australia; Seals Molecular Genetics, POW Hospital Campus, Barker Street, Randwick, Sydney, NSW 2031, Australia. Electronic address: e.kirk@unsw.edu.au.
UNSW Sydney · AUGarvan Institute of Medical Research · AUUniversity of Florida · USHunter Genetics · AUSydney Children's Hospital · AU

Funding

Amino Acid Regulation of Alternative SplicingR01DK092062 · NIDDK · UNIVERSITY OF FLORIDA · PI KILBERG, MICHAEL S. · 2011 to 2014
$1.3M
Amino Acid Regulation of the Fos/Jun Transcription FactorsR01DK094729 · NIDDK · UNIVERSITY OF FLORIDA · PI KILBERG, MICHAEL S. · 2011 to 2014
$1.2M
Asparagine Synthetase DeficiencyR21HD100576 · NICHD · UNIVERSITY OF FLORIDA · PI KILBERG, MICHAEL S. · 2020 to 2021
$419k
NICHD NIH HHS R21 HD100576NIDDK NIH HHS DK92062NIDDK NIH HHS DK94729NIDDK NIH HHS R01 DK092062NIDDK NIH HHS R01 DK094729
6 · The paper itself

Abstract

Asparagine Synthetase Deficiency is a recently described cause of profound intellectual disability, marked progressive cerebral atrophy and variable seizure disorder. To date there has been limited functional data explaining the underlying pathophysiology. We report a new case with compound heterozygous mutations in the ASNS gene (NM_183356.3:c. [866G>C]; [1010C>T]). Both variants alter evolutionarily conserved amino acids and were predicted to be pathogenic based on in silico protein modelling that suggests disruption of the critical ATP binding site of the ASNS enzyme. In patient fibroblasts, ASNS expression as well as protein and mRNA stability are not affected by these variants. However, there is markedly reduced proliferation of patient fibroblasts when cultured in asparagine-limited growth medium, compared to parental and wild type fibroblasts. Restricting asparagine replicates the physiology within the blood-brain-barrier, with limited transfer of dietary derived asparagine, resulting in reliance of neuronal cells on intracellular asparagine synthesis by the ASNS enzyme. These functional studies offer insight into the underlying pathophysiology of the dramatic progressive cerebral atrophy associated with Asparagine Synthetase Deficiency.

Indexed as

Cell ProliferationMutationAdenosine TriphosphateAsparagineAspartate-Ammonia LigaseBinding SitesCells, CulturedComputer SimulationCulture MediaExomeFemaleFibroblastsHumansIntellectual DisabilityMaleSequence Analysis, DNAAdenosine TriphosphateAsparagineAspartate-Ammonia LigaseCulture MediaAsparagineATP bindingEpileptic encephalopathyExome sequencingIntellectual disability

Identifiers

PMID26318253
PMCPMC10152381
OpenAlexW2135051922

What OpenQuestion holds

Textmetadata
LicenceTDM
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.