Evidence map›Paper›PMID 26005868›Full record

ArticleNature genetics2015

Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome.

Alicia Guemez-Gamboa, Long N Nguyen, Hongbo Yang, Maha S Zaki, Majdi Kara, Tawfeg Ben-Omran, Naiara Akizu, Rasim Ozgur Rosti, Basak Rosti, Eric Scott and 13 more

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

Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
143citing papers in PubMed, 1 pooled it
10.8field-weighted citation impact, top 1% 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

143 citing papers in PubMed, 1 synthesis or guideline pooled it, 211 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Cell-to-Cell Signaling Networks at the Blood-Brain Barrier in Health and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  4. Review
  5. Review
  6. MaternalNutrients · 2026
    Review
  7. Review
  8. Article
  9. Article
  10. Polyunsaturated fatty acid metabolism in the retinal pigment epithelium and its association with outer retinal disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Review
  11. Article
  12. Review
  13. Review
  14. Mfsd2a is important for maintaining epidermal homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  15. Review
  16. Article
  17. DHA elongates the neuronal primary cilium through GPR40-mediated signaling.Frontiers in cell and developmental biology · 2026
    Article
  18. Review
  19. Article
  20. Review

83 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

23 authors at 7 institutions in 4 countries.

Alicia Guemez-Gamboa1] Department of Neurosciences, University of California, San Diego, La Jolla, California, USA. [2] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
Long N NguyenSignature Research Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore.
Hongbo YangDepartment of Medicine, University of California, San Diego, La Jolla, California, USA.
Maha S ZakiClinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
Majdi KaraDepartment of Pediatrics, Tripoli Children's Hospital, Tripoli, Libya.
Tawfeg Ben-OmranClinical and Metabolic Genetics Division, Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar.
Naiara Akizu1] Department of Neurosciences, University of California, San Diego, La Jolla, California, USA. [2] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
Rasim Ozgur Rosti1] Department of Neurosciences, University of California, San Diego, La Jolla, California, USA. [2] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
Basak Rosti1] Department of Neurosciences, University of California, San Diego, La Jolla, California, USA. [2] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
Eric Scott1] Department of Neurosciences, University of California, San Diego, La Jolla, California, USA. [2] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
Jana Schroth1] Department of Neurosciences, University of California, San Diego, La Jolla, California, USA. [2] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
Brett Copeland1] Department of Neurosciences, University of California, San Diego, La Jolla, California, USA. [2] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
Keith K Vaux1] Department of Neurosciences, University of California, San Diego, La Jolla, California, USA. [2] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
Amaury Cazenave-GassiotDepartment of Biochemistry, National University of Singapore, Singapore.ORCID 000000023050634X
Debra Q Y QuekSignature Research Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore.
Bernice H WongSignature Research Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore.
Bryan C TanSignature Research Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore.
Markus R WenkDepartment of Biochemistry, National University of Singapore, Singapore.
Murat GunelYale Program on Neurogenetics, Departments of Neurosurgery, Neurobiology and Genetics, Yale University, School of Medicine, New Haven, Connecticut, USA.
Stacey GabrielBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Neil C ChiDepartment of Medicine, University of California, San Diego, La Jolla, California, USA.
David L SilverSignature Research Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore.
Joseph G Gleeson1] Department of Neurosciences, University of California, San Diego, La Jolla, California, USA. [2] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
Howard Hughes Medical Institute · USNational University of Singapore · SGUniversity of California San Diego · USBroad Institute · USHamad Medical Corporation · QANational Research Centre · EGYale University · US

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
Yale Center for Mendelian DisordersU54HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2012 to 2015
$11.0M
Project 3. Genetic Models of Human Structural Brain Defects in ZebrafishP01HD070494 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2011 to 2016
$6.7M
Molecular Characterization of Joubert SyndromeR01NS048453 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2004 to 2020
$6.0M
High Performance Computing Instrumentation for the Yale Center for Genome AnalysiS10OD018521 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2015 to 2015
$890k
Role of PCDH12 in neural circuit formation during brain development and diseaseK99NS089943 · NINDS · ROCKEFELLER UNIVERSITY · PI GUEMEZ GAMBOA, ALICIA DIONE · 2014 to 2015
$193k
Howard Hughes Medical InstituteNHGRI NIH HHS U54 HG003067NHGRI NIH HHS U54HG003067NHGRI NIH HHS U54 HG006504NHGRI NIH HHS U54HG006504NICHD NIH HHS P01 HD070494NICHD NIH HHS P01HD070494NIH HHS S10 OD018521NINDS NIH HHS K99 NS089943NINDS NIH HHS K99NS089943NINDS NIH HHS R01 NS048453NINDS NIH HHS R01NS048453
6 · The paper itself

Abstract

Docosahexanoic acid (DHA) is the most abundant omega-3 fatty acid in brain, and, although it is considered essential, deficiency has not been linked to disease. Despite the large mass of DHA in phospholipids, the brain does not synthesize it. DHA is imported across the blood-brain barrier (BBB) through the major facilitator superfamily domain-containing 2a (MFSD2A) protein. MFSD2A transports DHA as well as other fatty acids in the form of lysophosphatidylcholine (LPC). We identify two families displaying MFSD2A mutations in conserved residues. Affected individuals exhibited a lethal microcephaly syndrome linked to inadequate uptake of LPC lipids. The MFSD2A mutations impaired transport activity in a cell-based assay. Moreover, when expressed in mfsd2aa-morphant zebrafish, mutants failed to rescue microcephaly, BBB breakdown and lethality. Our results establish a link between transport of DHA and LPCs by MFSD2A and human brain growth and function, presenting the first evidence of monogenic disease related to transport of DHA in humans.

Indexed as

AdolescentAnimalsBiological TransportBlood-Brain BarrierBrainCase-Control StudiesChildChild, PreschoolConsanguinityFatty Acids, Omega-3FemaleGenes, LethalGenetic Association StudiesHEK293 CellsHumansInfantFatty Acids, Omega-3MFSD2A protein, humanSymportersTumor Suppressor Proteins

Identifiers

PMID26005868
PMCPMC4547531
OpenAlexW2166500841

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.