Mutant SNAP25B causes myasthenia, cortical hyperexcitability, ataxia, and intellectual disability.

ABSTRACT:

Objective

To identify and characterize the molecular basis of a syndrome associated with myasthenia, cortical hyperexcitability, cerebellar ataxia, and intellectual disability.

Methods

We performed in vitro microelectrode studies of neuromuscular transmission, performed exome and Sanger sequencing, and analyzed functional consequences of the identified mutation in expression studies.

Results

Neuromuscular transmission at patient endplates was compromised by reduced evoked quantal release. Exome sequencing identified a dominant de novo variant, p.Ile67Asn, in SNAP25B, a SNARE protein essential for exocytosis of synaptic vesicles from nerve terminals and of dense-core vesicles from endocrine cells. Ca(2+)-triggered exocytosis is initiated when synaptobrevin attached to

SUBMITTER: Shen XM 

PROVIDER: S-EPMC4277673 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature