Expanding the genotype and phenotype spectrum of SYT1-associated neurodevelopmental disorder.

ABSTRACT:

Purpose

Synaptotagmin-1 (SYT1) is a critical mediator of neurotransmitter release in the central nervous system. Previously reported missense SYT1 variants in the C2B domain are associated with severe intellectual disability, movement disorders, behavioral disturbances, and electroencephalogram abnormalities. In this study, we expand the genotypes and phenotypes and identify discriminating features of this disorder.

Methods

We describe 22 individuals with 15 de novo missense SYT1 variants. The evidence for pathogenicity is discussed, including the American College of Medical Genetics and Genomics/Association for Molecular Pathology criteria, known structure-function relationships, and molecular dynamics simulations. Quantitative behavioral data for 14 cases were compared wit

SUBMITTER: Melland H 

PROVIDER: S-EPMC8986325 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature