Journal article

Variants in SLC18A3, vesicular acetylcholine transporter, cause congenital myasthenic syndrome

GL O'Grady, C Verschuuren, M Yuen, R Webster, M Menezes, JM Fock, N Pride, HA Best, T Benavides Damm, C Turner, M Lek, AG Engel, KN North, NF Clarke, DG Macarthur, EJ Kamsteeg, ST Cooper

Neurology | LIPPINCOTT WILLIAMS & WILKINS | Published : 2016

Abstract

Objective: To describe the clinical and genetic characteristics of presynaptic congenital myasthenic syndrome secondary to biallelic variants in SLC18A3. Methods: Individuals from 2 families were identified with biallelic variants in SLC18A3, the gene encoding the vesicular acetylcholine transporter (VAChT), through whole-exome sequencing. Results: The patients demonstrated features seen in presynaptic congenital myasthenic syndrome, including ptosis, ophthalmoplegia, fatigable weakness, apneic crises, and deterioration of symptoms in cold water for patient 1. Both patients demonstrated moderate clinical improvement on pyridostigmine. Patient 1 had a broader phenotype, including learning dif..

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University of Melbourne Researchers

Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by National Human Genome Research Institute of the US National Institutes of Health


Awarded by National Institute of Health


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (grant numbers 1022707 to N.F.C. and K.N.N., 1031893 to N.F.C. and K.N.N., 1080587 to D.G.M., K.N.N., N.F.C., and S.T.C., 1056285 to G.L.O., and 1048816 to S.T.C.). Exome sequencing was supported by grants from the National Human Genome Research Institute of the US National Institutes of Health (Medical Sequencing Program grant U54 HG003067 to the Broad Institute principal investigator, Lander). Work done in Dr. Engel's laboratory was supported by National Institute of Health (grant number NS6277).