Please use this identifier to cite or link to this item: https://doi.org/10.1038/ng.3311
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dc.titleInactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome
dc.contributor.authorGuemez-Gamboa, Alicia
dc.contributor.authorNguyen, Long N
dc.contributor.authorYang, Hongbo
dc.contributor.authorZaki, Maha S
dc.contributor.authorKara, Majdi
dc.contributor.authorBen-Omran, Tawfeg
dc.contributor.authorAkizu, Naiara
dc.contributor.authorRosti, Rasim Ozgur
dc.contributor.authorRosti, Basak
dc.contributor.authorScott, Eric
dc.contributor.authorSchroth, Jana
dc.contributor.authorCopeland, Brett
dc.contributor.authorVaux, Keith K
dc.contributor.authorCazenave-Gassiot, Amaury
dc.contributor.authorQuek, Debra QY
dc.contributor.authorWong, Bernice H
dc.contributor.authorTan, Bryan C
dc.contributor.authorWenk, Markus R
dc.contributor.authorGunel, Murat
dc.contributor.authorGabriel, Stacey
dc.contributor.authorChi, Neil C
dc.contributor.authorSilver, David L
dc.contributor.authorGleeson, Joseph G
dc.date.accessioned2020-07-01T02:41:13Z
dc.date.available2020-07-01T02:41:13Z
dc.date.issued2015-07-01
dc.identifier.citationGuemez-Gamboa, Alicia, Nguyen, Long N, Yang, Hongbo, Zaki, Maha S, Kara, Majdi, Ben-Omran, Tawfeg, Akizu, Naiara, Rosti, Rasim Ozgur, Rosti, Basak, Scott, Eric, Schroth, Jana, Copeland, Brett, Vaux, Keith K, Cazenave-Gassiot, Amaury, Quek, Debra QY, Wong, Bernice H, Tan, Bryan C, Wenk, Markus R, Gunel, Murat, Gabriel, Stacey, Chi, Neil C, Silver, David L, Gleeson, Joseph G (2015-07-01). Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome. NATURE GENETICS 47 (7) : 809-813. ScholarBank@NUS Repository. https://doi.org/10.1038/ng.3311
dc.identifier.issn10614036
dc.identifier.issn15461718
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/170831
dc.description.abstract© 2015 Nature America, Inc. All rights reserved. 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.
dc.language.isoen
dc.publisherNATURE PUBLISHING GROUP
dc.sourceElements
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectGenetics & Heredity
dc.subjectFATTY-ACID COMPOSITION
dc.subjectDOCOSAHEXAENOIC ACID
dc.subjectBARRIER
dc.subjectPERICYTES
dc.subjectNEUROGENESIS
dc.subjectEXPRESSION
dc.subjectDISCOVERY
dc.subjectMOUSE
dc.typeArticle
dc.date.updated2020-06-17T03:33:28Z
dc.contributor.departmentDEPT OF BIOCHEMISTRY
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1038/ng.3311
dc.description.sourcetitleNATURE GENETICS
dc.description.volume47
dc.description.issue7
dc.description.page809-813
dc.description.placeUnited States
dc.published.statePublished
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