De novo variants in CAMK2A and CAMK2B cause neurodevelopmental disorders.

ABSTRACT:

Objective

α (CAMK2A) and β (CAMK2B) isoforms of Calcium/calmodulin-dependent protein kinase II (CaMKII) play a pivotal role in neuronal plasticity and in learning and memory processes in the brain. Here, we explore the possible involvement of α- and β-CaMKII variants in neurodevelopmental disorders.

Methods

Whole-exome sequencing was performed for 976 individuals with intellectual disability, developmental delay, and epilepsy. The effect of CAMK2A and CAMK2B variants on CaMKII structure and firing of neurons was evaluated by computational structural analysis, immunoblotting, and electrophysiological analysis.

Results

We identified a total of five de novo CAMK2A and CAMK2B variants in three and two i

SUBMITTER: Akita T 

PROVIDER: S-EPMC5846454 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature