Biallelic intragenic duplication in ADGRB3 (BAI3) gene associated with intellectual disability, cerebellar atrophy, and behavioral disorder

• Published in: European journal of human genetics : EJHG 2019-04, Vol.27 (4), p.594-602
• Main Authors: Scuderi, Carmela, Saccuzzo, Lucia, Vinci, Mirella, Castiglia, Lucia, Galesi, Ornella, Salemi, Michele, Mattina, Teresa, Borgione, Eugenia, Città, Santina, Romano, Corrado, Fichera, Marco
• Format: Article
• Language: English
• Subjects: Adult; Aged; Ataxia; Atrophy; Atrophy - genetics; Atrophy - physiopathology; Axon guidance; Central nervous system; Cerebellar Ataxia - genetics; Cerebellar Ataxia - physiopathology; Cerebellum; Cognitive ability; Consanguinity; Copy number; DNA Copy Number Variations - genetics; DNA microarrays; Female; G protein-coupled receptors; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Intellectual disabilities; Intellectual Disability - genetics; Intellectual Disability - physiopathology; Male; Mental disorders; Middle Aged; Myelination; Nerve Tissue Proteins - genetics; Neurodevelopmental disorders; Polymorphism, Single Nucleotide - genetics; Siblings; Single-nucleotide polymorphism; Synapses; Synaptogenesis
• ISSN: 1018-4813; 1476-5438; 1476-5438
• DOI: 10.1038/s41431-018-0321-1

In recent years, chromosomal microarray analysis has permitted the discovery of rearrangements underlying several neurodevelopmental disorders and still represents the first diagnostic test for unexplained neurodevelopmental disabilities. Here we report a family of consanguineous parents showing psychiatric disorders and their two sons both affected by intellectual disability, ataxia, and behavioral disorder. SNP/CGH array analysis in this family demonstrated in both siblings a biallelic duplication inherited from the heterozygous parents, disrupting the ADGRB3 gene. ADGRB3, also known as BAI3, belongs to the subfamily of adhesion G protein-coupled receptors (adhesion GPCRs) that regulate many aspects of the central nervous system, including axon guidance, myelination, and synapse formation. Single nucleotide polymorphisms and copy number variants involving ADGRB3 have recently been associated with psychiatric disorders. These findings further support this association and also suggest that biallelic variants affecting the function of the ADGRB3 gene may also cause cognitive impairments and ataxia.