Heterozygous and homozygous variants in STX1A cause a neurodevelopmental disorder with or without epilepsy.

ABSTRACT: The neuronal SNARE complex drives synaptic vesicle exocytosis. Therefore, one of its core proteins syntaxin 1A (STX1A) has long been suspected to play a role in neurodevelopmental disorders. We assembled eight individuals harboring ultra rare variants in STX1A who present with a spectrum of intellectual disability, autism and epilepsy. Causative variants comprise a homozygous splice variant, three de novo missense variants and two inframe deletions of a single amino acid. We observed a phenotype mainly driven by epilepsy in the individuals with missense variants in contrast to intellectual disability and autistic behavior in individuals with single amino acid deletions and the splicing variant. In silico modeling of missense variants and single amino acid deletions show different impaired

SUBMITTER: Luppe J 

PROVIDER: S-EPMC9995539 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature