Highly fatal fast-channel syndrome caused by AChR ε subunit mutation at the agonist binding site.

ABSTRACT:

Objective

To characterize the molecular basis of a novel fast-channel congenital myasthenic syndrome.

Methods

We used the candidate gene approach to identify the pathogenic mutation in the acetylcholine receptor (AChR) ε subunit, genetically engineered the mutant AChR into HEK cells, and evaluated the level of expression and kinetic properties of the mutant receptor.

Results

An 8-year-old boy born to consanguineous parents had severe myasthenic symptoms since birth. He is wheelchair bound and pyridostigmine therapy enables him to take only a few steps. Three similarly affected siblings died in infancy. He carries a homozygous p.W55R mutation at the α/ε subunit interface of the AChR agonist binding site. The mutant protein expresses well in HEK cells. Patch-clamp analy

SUBMITTER: Shen XM 

PROVIDER: S-EPMC3405251 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature