The University of Southampton
University of Southampton Institutional Repository

Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans

Ohno, Kinji, Tsujino, Akira, Brengman, Joan M., Harper, C. Michel, Bajzer, Zeljko, Udd, Bjarne, Beyring, Roger, Robb, Stephanie, Kirkham, Fenella J. and Engel, Andrew G. (2001) Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans Proceedings of the National Academy of Sciences, 98, (4), pp. 2017-2022.

Record type: Article

Abstract

Choline acetyltransferase (ChAT; EC 2.3.1.6) catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses. Mutations in genes encoding ChAT affecting motility exist in Caenorhabditis elegans and Drosophila, but no CHAT mutations have been observed in humans to date. Here we report that mutations in CHAT cause a congenital myasthenic syndrome associated with frequently fatal episodes of apnea (CMS-EA). Studies of the neuromuscular junction in this disease show a stimulation-dependent decrease of the amplitude of the miniature endplate potential and no deficiency of the ACh receptor. These findings point to a defect in ACh resynthesis or vesicular filling and to CHAT as one of the candidate genes. Direct sequencing of CHAT reveals 10 recessive mutations in five patients with CMS-EA. One mutation (523insCC) is a frameshifting null mutation. Three mutations (I305T, R420C, and E441K) markedly reduce ChAT expression in COS cells. Kinetic studies of nine bacterially expressed ChAT mutants demonstrate that one mutant (E441K) lacks catalytic activity, and eight mutants (L210P, P211A, I305T, R420C, R482G, S498L, V506L, and R560H) have significantly impaired catalytic efficiencies.

Full text not available from this repository.

More information

Published date: 2001
Organisations: Clinical Neurosciences

Identifiers

Local EPrints ID: 27679
URI: http://eprints.soton.ac.uk/id/eprint/27679
ISSN: 0027-8424
PURE UUID: 64bb40b4-a24f-4c93-a6a9-7fb7adf4fa30

Catalogue record

Date deposited: 27 Apr 2006
Last modified: 17 Jul 2017 16:04

Export record

Contributors

Author: Kinji Ohno
Author: Akira Tsujino
Author: Joan M. Brengman
Author: C. Michel Harper
Author: Zeljko Bajzer
Author: Bjarne Udd
Author: Roger Beyring
Author: Stephanie Robb
Author: Fenella J. Kirkham
Author: Andrew G. Engel

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.

×