Variants in GNAI1 cause a syndrome associated with variable features including developmental delay, seizures, and...

Area of Science:

• Genetics
• Neuroscience
• Molecular Biology

Background:

• Neurodevelopmental disorders (NDDs) are a heterogeneous group of genetic conditions.
• Common NDD features include developmental delay, intellectual disability, and autism spectrum disorders.

Purpose of the Study:

• To define the molecular and phenotypic spectrum of neurodevelopmental disorders caused by variants in the GNAI1 gene.

Main Methods:

• Utilized large cohort trio-based exome sequencing.
• Collected genotype and phenotype data from 24 unrelated individuals with NDDs and GNAI1 variants.
• Facilitated international data-sharing for comprehensive analysis.

Main Results:

• Identified 16 unique GNAI1 variants in 24 affected individuals.
• 23 variants were de novo, and 1 was inherited from a mosaic parent.
• Core features observed include global developmental delay, intellectual disability, hypotonia, and epilepsy.

Conclusions:

• Establishes GNAI1 variants as a cause of neurodevelopmental disorders.
• GNAI1-related NDDs typically present with severe delays, hypotonia, and epilepsy.
• Phenotypic variability includes behavioral issues and mild dysmorphic features.