ADGRB3 is a member of a subfamily of adhesion G protein-coupled receptors (adhesion GPCRs) that play a key role in the regulation of several aspects of the central nervous system, such as axon guidance, myelination, and synapse formation and function.
A unique homozygous pathogenic variant consisting in an intragenic tandem duplication involving several exons of the ADGRB3 gene has been identified up to now in a consanguineous family. This duplication is predicted to result in an abnormal out-of-frame transcript leading to loss of protein function. In line with previous clinical descriptions of individuals carrying SNPs and copy number variations (CNVs) within this gene, heterozygous parents in this family showed neuropsychiatric symptoms of the disease. Direct sequencing of ADGRB3 or whole exome sequencing, may capture homozygous or compound heterozygous pathogenic variants in patients showing clinical picture that may be associated with ADRGB3 defects. However, as a homozygous CNV has been identified, quantitative tests such as multiplex ligation-dependent probe amplification (MLPA) or real-time PCR should also be performed to identify pathogenic gene rearrangements that could be overlook by sequence analysis.
ADGRB3