Our Latest Scientific News
Novel GNB1 mutations disrupt assembly and function of G protein heterotrimers and cause global developmental delay in humans
Global developmental delay (GDD), often accompanied by intellectual disability, seizures and other features is a severe, clinically and genetically highly heterogeneous childhood-onset disorder. In cases where genetic causes have been identified, de-novo mutations in neuronally expressed genes are a common scenario. These mutations can be best identified by exome sequencing of parent-offspring trios. De novo mutations in the guanine nucleotide-binding protein, beta 1 (GNB1) gene, encoding the Gβ1 subunit of heterotrimeric G proteins, have recently been identified as a novel genetic cause of GDD.
A study was conducted using whole exome sequencing (WES) to identify underlying pathogenic variants, or likely pathogenic variants, in 1,000 diagnostic cases from 54 different countries. Patients selected displayed a wide variety in the number, nature and severity of symptoms. Clinical information given by the requesting physicians was translated to HPO terms and WES was performed on patient samples according to standardized settings.
"The ability to discover genetic variants in a patient runs far ahead of the ability to interpret them. Databases with accurate descriptions of the causal relationship between the variants and the phenotype are valuable since these are critical tools in clinical genetic diagnostics. Here, we introduce a comprehensive and global genotype–phenotype database focusing on rare diseases."