Haploinsufficiency as a disease mechanism in GNB1-associated neurodevelopmental disorder.

ABSTRACT:

Background

GNB1 encodes a subunit of a heterotrimeric G-protein complex that transduces intracellular signaling cascades. Disruptions to the gene have previously been shown to be embryonic lethal in knockout mice and to cause complex neurodevelopmental disorders in humans. To date, the majority of variants associated with disease in humans have been missense variants in exons 5-7.

Methods

Genetic sequencing was performed on two patients presenting with complex neurological phenotypes including intellectual disability, hypotonia, and in one patient seizures. Reported variants were assessed using RNA sequencing and functional BRET/BiFC assays.

Results

A splice variant reported in patient 1 was confirmed to cause usage of a cryptic splice site leading to a truncated prot

SUBMITTER: Schultz-Rogers L 

PROVIDER: S-EPMC7667315 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature