De novo mutations in KIF1A cause progressive encephalopathy and brain atrophy.

ABSTRACT:

Objective

To determine the cause and course of a novel syndrome with progressive encephalopathy and brain atrophy in children.

Methods

Clinical whole-exome sequencing was performed for global developmental delay and intellectual disability; some patients also had spastic paraparesis and evidence of clinical regression. Six patients were identified with de novo missense mutations in the kinesin gene KIF1A. The predicted functional disruption of these mutations was assessed in silico to compare the calculated conformational flexibility and estimated efficiency of ATP binding to kinesin motor domains of wild-type (WT) versus mutant alleles. Additionally, an in vitro microtubule gliding assay was performed to assess the effects of de novo dominant, inherited recessive, and polym

SUBMITTER: Esmaeeli Nieh S 

PROVIDER: S-EPMC4479523 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature