Haploinsufficiency of the Notch Ligand DLL1 Causes Variable Neurodevelopmental Disorders.

ABSTRACT: Notch signaling is an established developmental pathway for brain morphogenesis. Given that Delta-like 1 (DLL1) is a ligand for the Notch receptor and that a few individuals with developmental delay, intellectual disability, and brain malformations have microdeletions encompassing DLL1, we hypothesized that insufficiency of DLL1 causes a human neurodevelopmental disorder. We performed exome sequencing in individuals with neurodevelopmental disorders. The cohort was identified using known Matchmaker Exchange nodes such as GeneMatcher. This method identified 15 individuals from 12 unrelated families with heterozygous pathogenic DLL1 variants (nonsense, missense, splice site, and one whole gene deletion). The most common features in our cohort were intellectual disability, autism spectrum dis

SUBMITTER: Fischer-Zirnsak B 

PROVIDER: S-EPMC6731356 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature