A novel fast-channel myasthenia caused by mutation in β subunit of AChR reveals subunit-specific contribution of the intracellular M1-M2 linker to channel gating.

ABSTRACT: Genetic variants causing the fast-channel congenital myasthenic syndrome (CMS) have been identified in the α, δ, and ε but not the β subunit of acetylcholine receptor (AChR). A 16-year-old girl with severe myasthenia had low-amplitude and fast-decaying miniature endplate potentials. Mutation analysis revealed two heteroallelic variants in CHRNB1 encoding the AChR β subunit: a novel c.812C>T (p.P248L) variant in M1-M2 linker (p.P271L in HGVS nomenclature), and a ~430 bp deletion causing loss of exon 8 leading to frame-shift and a premature stop codon (p.G251Dfs*21). P248 is conserved in all β subunits of different species, but not in other AChR subunits. Measurements of radio-labeled α-bungarotoxin binding show that βP248L reduces AChR expression to 60% of wild-type. Patch clamp recordings

SUBMITTER: Shen XM 

PROVIDER: S-EPMC7483818 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature