Impaired gating of γ- and ε-AChR respectively causes Escobar syndrome and fast-channel myasthenia.

ABSTRACT:

Objective

To dissect the kinetic defects of acetylcholine receptor (AChR) γ subunit variant in an incomplete form of the Escobar syndrome without pterygium and compare it with those of a variant of corresponding residue in the AChR ε subunit in a congenital myasthenic syndrome (CMS).

Methods

Whole exome sequencing, α-bungarotoxin binding assay, single channel patch-clamp recordings, and maximum likelihood analysis of channel kinetics.

Results

We identified compound heterozygous variants in AChR γ and ε subunits in three Escobar syndrome (1-3) and three CMS patients (4-6), respectively. Each Escobar syndrome patient carries γP121R along with γV221Afs*44 in patients 1 and 2, and γY63* in patient 3. Three CMS patients share εP121T along with εR20W, εG-8R, and εY15H in pa

SUBMITTER: Shen XM 

PROVIDER: S-EPMC10187723 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature