@article{7700696fc4a44e649c60c5024c47573e,
title = "Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome",
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.",
author = "Alicia Guemez-Gamboa and Nguyen, {Long N.} and Hongbo Yang and Zaki, {Maha S.} and Majdi Kara and Tawfeg Ben-Omran and Naiara Akizu and Rosti, {Rasim Ozgur} and Basak Rosti and Eric Scott and Jana Schroth and Brett Copeland and Vaux, {Keith K.} and Amaury Cazenave-Gassiot and Quek, {Debra Q.Y.} and Wong, {Bernice H.} and Tan, {Bryan C.} and Wenk, {Markus R.} and Murat Gunel and Stacey Gabriel and Chi, {Neil C.} and Silver, {David L.} and Gleeson, {Joseph G.}",
note = "Funding Information: This work was supported by grants from the US National Institutes of Health, including P01HD070494 (to J.G.G. and N.C.C.), R01NS048453 (to J.G.G.), K99NS089943 (to A.G.-G.), and U54HG003067 to the Broad Institute and U54HG006504 to the Yale Center for Mendelian Disorders (M.G.), grant CBRG/069/2014 from the Singapore Ministry of Health{\textquoteright}s National Medical Research Council (to D.L.S.), Singapore National Research Foundation Competitive Research Program grant 2007-04 (to M.R.W.) and the National University of Singapore{\textquoteright}s Life Sciences Institute (to M.R.W.). Sequencing was provided in part by a gift from BGI to Rady Children{\textquoteright}s Hospital, San Diego for undiagnosed patients. Human brain samples were provided by S. Roy (University of California, San Diego). Publisher Copyright: {\textcopyright} 2015 Nature America, Inc. All rights reserved.",
year = "2015",
month = jun,
day = "26",
doi = "10.1038/ng.3311",
language = "English (US)",
volume = "47",
pages = "809--813",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "7",
}
