Bonora and colleagues have recently identified an intragenic deletion of maternal origin in two siblings with intellectual disability (ID) and epilepsy in the CADPS2 gene, encoding for a synaptic protein involved in neurotrophin release and interaction with dopamine receptor type 2 (D2DR). They next screened 223 additional patients with ID and autism spectrum disorder and identified a missense change of maternal origin disrupting CADPS2/D2DR interaction. CADPS2 allelic expression was tested in blood and different adult human brain regions, revealing that the gene was monoallelically expressed in blood and amygdala, and the expressed allele was the one of maternal origin. Cadps2 gene expression performed in mice at different developmental stages was biallelic in the postnatal and adult stages; however, a monoallelic (maternal) expression was detected in the embryonal stage, suggesting that CADPS2 is subjected to tissue- and temporal-specific regulation in human and mice.
Posted by Nicola Brunetti-Pierri, MD, FACMG