Please use this identifier to cite or link to this item: https://doi.org/10.1038/ng.3311
Title: Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome
Authors: Guemez-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
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
FATTY-ACID COMPOSITION
DOCOSAHEXAENOIC ACID
BARRIER
PERICYTES
NEUROGENESIS
EXPRESSION
DISCOVERY
MOUSE
Issue Date: 1-Jul-2015
Publisher: NATURE PUBLISHING GROUP
Citation: Guemez-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
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.
Source Title: NATURE GENETICS
URI: https://scholarbank.nus.edu.sg/handle/10635/170831
ISSN: 10614036
15461718
DOI: 10.1038/ng.3311
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