Evidence map›Paper›PMID 27213289›Full record

ArticleNature genetics2016

NANS-mediated synthesis of sialic acid is required for brain and skeletal development.

Clara D M van Karnebeek, Luisa Bonafé, Xiao-Yan Wen, Maja Tarailo-Graovac, Sara Balzano, Beryl Royer-Bertrand, Angel Ashikov, Livia Garavelli, Isabella Mammi, Licia Turolla and 36 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Nature genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 96 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed, 1 pooled it
8.9field-weighted citation impact, top 2% 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

96 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Sialylation in the nervous system: Functions and mechanisms.The Journal of biological chemistry · 2026
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Microbial Production ofFoods (Basel, Switzerland) · 2025
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. A biallelic variant inLife science alliance · 2025
    Article
  17. Article
  18. Review
  19. Review
  20. The Multi-Omic Approach to Newborn Screening: Opportunities and Challenges.International journal of neonatal screening · 2024
    Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

46 authors at 14 institutions in 8 countries.

Clara D M van KarnebeekDepartment of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
Luisa BonaféCentre for Molecular Diseases, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
Xiao-Yan WenZebrafish Centre for Advanced Drug Discovery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada.
Maja Tarailo-GraovacCentre for Molecular Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Sara BalzanoDepartment of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
Beryl Royer-BertrandCentre for Molecular Diseases, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
Angel AshikovDepartment of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
Livia GaravelliClinical Genetics Unit, IRCCS-S. Maria Nuova Hospital, Reggio Emilia, Italy.
Isabella MammiAmbulatorio di Genetica Medica ULSS 13, U.O. Ginecologia e Ostetricia, Ospedale Dolo, Dolo, Italy.
Licia TurollaMedical Genetics Unit, Local Health Authority (ULSS 9), Treviso, Italy.
Catherine BreenManchester Centre for Genomic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Dian DonnaiManchester Centre for Genomic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Valérie Cormier-DaireInstitut IMAGINE, Hôpital Necker-Enfants Malades, Paris, France.
Delphine HeronAmbulatorio di Genetica Medica ULSS 13, U.O. Ginecologia e Ostetricia, Ospedale Dolo, Dolo, Italy.
Gen NishimuraDepartment of Radiology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
Shinichi UchikawaDepartment of Orthopedics, National Center for Child Health and Development, Tokyo, Japan.
Belinda Campos-XavierCentre for Molecular Diseases, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.
Antonio RossiDepartment of Molecular Medicine, Unit of Biochemistry, University of Pavia, Pavia, Italy.
Thierry HennetDepartment of Physiology, University of Zürich, Zurich, Switzerland.
Koroboshka Brand-ArzamendiZebrafish Centre for Advanced Drug Discovery, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada.
Jacob RozmusDepartment of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
Keith HarshmanGenomic Technologies Facility, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
Brian J StevensonVital-IT Group, Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland.
Enrico GirardiCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0003-3508-2723
Giulio Superti-FurgaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0002-0570-1768
Tammie DewanDepartment of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
Alissa CollingridgeDepartment of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
Jessie HalparinDepartment of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
Colin J RossDepartment of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
Margot I Van AllenDepartment of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Andrea RossiNeuroradiology Department, G. Gaslini Children's Hospital, Genoa, Italy.
Udo F EngelkeTranslational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
Leo A J KluijtmansTranslational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
Ed van der HeeftTranslational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
Herma RenkemaTranslational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
Arjan de BrouwerDepartment of Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Karin HuijbenTranslational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
Fokje ZijlstraTranslational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
Torben HeiseDepartment of Organic Chemistry, Radboud University, Nijmegen, the Netherlands.
Thomas BoltjeDepartment of Organic Chemistry, Radboud University, Nijmegen, the Netherlands.
Wyeth W WassermanCentre for Molecular Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Carlo RivoltaDepartment of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
Sheila UngerMedical Genetics Service, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
Dirk J LefeberDepartment of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
Ron A WeversTranslational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
Andrea Superti-FurgaCentre for Molecular Diseases, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.ORCID 0000-0002-3543-7531
Radboud University Nijmegen · NLUniversity of British Columbia · CAUniversity of Lausanne · CHAustrian Academy of Sciences · ATManchester Academic Health Science Centre · GBSt. Michael's Hospital · CAUniversity of Pavia · ITHôpital Necker-Enfants Malades · FRNational Center For Child Health and Development · JPSanta Maria Nuova Hospital · ITSIB Swiss Institute of Bioinformatics · CHSorbonne Université · FRTokyo Metropolitan Children's Medical Center · JPUniversity of Zurich · CH

Funding

CIHR 301221
6 · The paper itself

Abstract

We identified biallelic mutations in NANS, the gene encoding the synthase for N-acetylneuraminic acid (NeuNAc; sialic acid), in nine individuals with infantile-onset severe developmental delay and skeletal dysplasia. Patient body fluids showed an elevation in N-acetyl-D-mannosamine levels, and patient-derived fibroblasts had reduced NANS activity and were unable to incorporate sialic acid precursors into sialylated glycoproteins. Knockdown of nansa in zebrafish embryos resulted in abnormal skeletal development, and exogenously added sialic acid partially rescued the skeletal phenotype. Thus, NANS-mediated synthesis of sialic acid is required for early brain development and skeletal growth. Normal sialylation of plasma proteins was observed in spite of NANS deficiency. Exploration of endogenous synthesis, nutritional absorption, and rescue pathways for sialic acid in different tissues and developmental phases is warranted to design therapeutic strategies to counteract NANS deficiency and to shed light on sialic acid metabolism and its implications for human nutrition.

Indexed as

AdultAge of OnsetAnimalsBone Diseases, DevelopmentalBrainChild, PreschoolDevelopmental DisabilitiesEmbryo, NonmammalianFemaleFibroblastsHumansInfantInfant, NewbornMaleMetabolism, Inborn ErrorsMutationN-acylneuraminate-9-phosphate synthaseOxo-Acid-LyasesSialic Acids

Identifiers

PMID27213289
OpenAlexW2398435542

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.