Slow-channel myasthenia due to novel mutation in M2 domain of AChR delta subunit.

ABSTRACT:

Objective

To characterize the molecular and phenotypic basis of a severe slow-channel congenital myasthenic syndrome (SCCMS).

Methods

Intracellular and single-channel recordings from patient endplates; alpha-bungarotoxin binding studies; direct sequencing of AChR genes; microsatellite analysis; kinetic analysis of AChR activation; homology modeling of adult human AChR structure.

Results

Among 24 variants reported to cause SCCMS only two appear in the AChR δ-subunit. We here report a 16-year-old patient harboring a novel δL273F mutation (δL294F in HGVS nomenclature) in the second transmembrane domain (M2) of the AChR δ subunit. Kinetic analyses with ACh and the weak agonist choline indicate that δL273F prolongs the channel opening bursts 9.4-fold due to a 75-fold incre

SUBMITTER: Shen XM 

PROVIDER: S-EPMC6801167 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature