The University of Southampton
University of Southampton Institutional Repository

A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome

A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome
A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome
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
1061-4036
814-817
Alakbarzade, Vafa
fca562a5-1ec0-498c-9786-f65ca4aebb88
Hameed, Abdul
81fad2d2-2d53-431e-9fbc-c640ec80ed9c
Quek, Debra Q.Y.
7cc5021a-53a3-43cb-a8a8-4d52f14ad918
Chioza, Barry A
6a2a333c-dc72-4ef7-bfcc-ad3bd079456b
Baple, Emma L.
3069a362-2742-42a5-a7a7-e92a9af6fa88
Cazenave-Gassiot, Amaury
f53d5438-9fad-4fd6-98f9-3e289205dcd7
Nguyen, Long N.
56ba58b1-3271-4f5c-9f71-e7442ae61cda
Wenk, Markus R.
d1ba356f-b0ed-4318-886a-c8f929679060
Ahmad, Arshia Q.
0d49168a-1a09-476e-9973-c5cf697d8f78
Sreekantan-Nair, Ajith
568e3c9e-4033-4360-bd52-7e67d143d5d2
Weedon, Michael N.
4ea46048-ef8b-4052-8ff6-a40cf8f5a913
Rich, Phil
3208ca25-e163-4b00-aeed-c84561e8d199
Patton, Michael A.
6a9dcfa4-8434-4102-9b2b-6ab4d510a04d
Warner, Thomas T.
677915c3-cb5f-4e76-a813-8b1d0781886b
Silver, David L.
2a691ed3-b6c8-4b7f-80a6-28e8cccfaa05
Crosby, Andrew H.
241bc220-d13f-4d1c-8d2b-47ed6fa5cbbd
Alakbarzade, Vafa
fca562a5-1ec0-498c-9786-f65ca4aebb88
Hameed, Abdul
81fad2d2-2d53-431e-9fbc-c640ec80ed9c
Quek, Debra Q.Y.
7cc5021a-53a3-43cb-a8a8-4d52f14ad918
Chioza, Barry A
6a2a333c-dc72-4ef7-bfcc-ad3bd079456b
Baple, Emma L.
3069a362-2742-42a5-a7a7-e92a9af6fa88
Cazenave-Gassiot, Amaury
f53d5438-9fad-4fd6-98f9-3e289205dcd7
Nguyen, Long N.
56ba58b1-3271-4f5c-9f71-e7442ae61cda
Wenk, Markus R.
d1ba356f-b0ed-4318-886a-c8f929679060
Ahmad, Arshia Q.
0d49168a-1a09-476e-9973-c5cf697d8f78
Sreekantan-Nair, Ajith
568e3c9e-4033-4360-bd52-7e67d143d5d2
Weedon, Michael N.
4ea46048-ef8b-4052-8ff6-a40cf8f5a913
Rich, Phil
3208ca25-e163-4b00-aeed-c84561e8d199
Patton, Michael A.
6a9dcfa4-8434-4102-9b2b-6ab4d510a04d
Warner, Thomas T.
677915c3-cb5f-4e76-a813-8b1d0781886b
Silver, David L.
2a691ed3-b6c8-4b7f-80a6-28e8cccfaa05
Crosby, Andrew H.
241bc220-d13f-4d1c-8d2b-47ed6fa5cbbd

Alakbarzade, Vafa, Hameed, Abdul, Quek, Debra Q.Y., 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. and Crosby, Andrew H. (2015) A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome. Nature Genetics, 47 (7), 814-817. (doi:10.1038/ng.3313). (PMID:26005865)

Record type: Article

Abstract

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

Full text not available from this repository.

More information

Accepted/In Press date: 1 May 2015
e-pub ahead of print date: 25 May 2015
Published date: July 2015
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 377539
URI: http://eprints.soton.ac.uk/id/eprint/377539
ISSN: 1061-4036
PURE UUID: 91ccb94b-ad29-4a31-a9ee-3669e4357be3

Catalogue record

Date deposited: 12 Jun 2015 09:20
Last modified: 15 Jul 2019 21:17

Export record

Altmetrics

Contributors

Author: Vafa Alakbarzade
Author: Abdul Hameed
Author: Debra Q.Y. Quek
Author: Barry A Chioza
Author: Emma L. Baple
Author: Amaury Cazenave-Gassiot
Author: Long N. Nguyen
Author: Markus R. Wenk
Author: Arshia Q. Ahmad
Author: Ajith Sreekantan-Nair
Author: Michael N. Weedon
Author: Phil Rich
Author: Michael A. Patton
Author: Thomas T. Warner
Author: David L. Silver
Author: Andrew H. Crosby

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×