Maternally inherited genetic variants of CADPS2 are present in autism spectrum disorders and intellectual disability patients.

EMBO molecular medicine 2014 Jun

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Intellectual disability (ID) and autism spectrum disorders (ASDs) are complex neuropsychiatric conditions, with overlapping clinical boundaries in many patients. We identified a novel intragenic deletion of maternal origin in two siblings with mild ID and epilepsy in the CADPS2 gene, encoding for a synaptic protein involved in neurotrophin release and interaction with dopamine receptor type 2 (D2DR). Mutation screening of 223 additional patients (187 with ASD and 36 with ID) 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. We suggest that CADPS2 variants may contribute to ID/ASD development, possibly through a parent-of-origin effect. © 2014 The Authors. Published under the terms of the CC BY license.

Citation

Elena Bonora, Claudio Graziano, Fiorella Minopoli, Elena Bacchelli, Pamela Magini, Chiara Diquigiovanni, Silvia Lomartire, Francesca Bianco, Manuela Vargiolu, Piero Parchi, Elena Marasco, Vilma Mantovani, Luca Rampoldi, Matteo Trudu, Antonia Parmeggiani, Agatino Battaglia, Luigi Mazzone, Giada Tortora, IMGSAC, Elena Maestrini, Marco Seri, Giovanni Romeo. Maternally inherited genetic variants of CADPS2 are present in autism spectrum disorders and intellectual disability patients. EMBO molecular medicine. 2014 Jun;6(6):795-809