Please use this identifier to cite or link to this item: https://doi.org/10.1038/ng.3313
Title: A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome
Authors: Alakbarzade, Vafa
Hameed, Abdul
Quek, Debra QY
Chioza, Barry A
Baple, Emma L
Cazenave-Gassiot, Amaury
Nguyen, Long N
Wenk, Markus R 
Ahmad, Arshia Q
Sreekantan-Nair, Ajith
Weedon, Michael N
Rich, Phil
Patton, Michael A
Warner, Thomas T
Silver, David L
Crosby, Andrew H
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
RAT
Issue Date: 26-Jun-2015
Publisher: NATURE PUBLISHING GROUP
Citation: Alakbarzade, Vafa, Hameed, Abdul, Quek, Debra QY, Chioza, Barry A, Baple, Emma L, Cazenave-Gassiot, Amaury, Nguyen, Long N, Wenk, Markus R, Ahmad, Arshia Q, Sreekantan-Nair, Ajith, Weedon, Michael N, Rich, Phil, Patton, Michael A, Warner, Thomas T, Silver, David L, Crosby, Andrew H (2015-06-26). A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome. NATURE GENETICS 47 (7) : 814-817. ScholarBank@NUS Repository. https://doi.org/10.1038/ng.3313
Abstract: © 2015 Nature America, Inc. All rights reserved. The major pathway by which the brain obtains essential omega-3 fatty acids from the circulation is through a sodium-dependent lysophosphatidylcholine (LPC) transporter (MFSD2A), expressed in the endothelium of the blood-brain barrier. Here we show that a homozygous mutation affecting a highly conserved MFSD2A residue (p.Ser339Leu) is associated with a progressive microcephaly syndrome characterized by intellectual disability, spasticity and absent speech. We show that the p.Ser339Leu alteration does not affect protein or cell surface expression but rather significantly reduces, although not completely abolishes, transporter activity. Notably, affected individuals displayed significantly increased plasma concentrations of LPCs containing mono- and polyunsaturated fatty acyl chains, indicative of reduced brain uptake, confirming the specificity of MFSD2A for LPCs having mono-and polyunsaturated fatty acyl chains. Together, these findings indicate an essential role for LPCs in human brain development and function and provide the first description of disease associated with aberrant brain LPC transport in humans.
Source Title: NATURE GENETICS
URI: https://scholarbank.nus.edu.sg/handle/10635/170830
ISSN: 10614036
15461718
DOI: 10.1038/ng.3313
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