Open AccessMaternally inherited genetic variants of CADPS 2 are present in Autism Spectrum Disorders and Intellectual Disability patients
Author(s) -
Bonora Elena,
Graziano Claudio,
Minopoli Fiorella,
Bacchelli Elena,
Magini Pamela,
Diquigiovanni Chiara,
Lomartire Silvia,
Bianco Francesca,
Vargiolu Manuela,
Parchi Piero,
Marasco Elena,
Mantovani Vilma,
Rampoldi Luca,
Trudu Matteo,
Parmeggiani Antonia,
Battaglia Agatino,
Mazzone Luigi,
Tortora Giada,
Maestrini Elena,
Seri Marco,
Romeo Giovanni
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201303235
Subject(s) - autism , missense mutation , intellectual disability , epilepsy , genetics , biology , allele , gene , autism spectrum disorder , mutation , neuroscience , psychology , psychiatry
Intellectual disability ( ID ) and autism spectrum disorders ( ASD s) 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 CADPS 2 gene, encoding for a synaptic protein involved in neurotrophin release and interaction with dopamine receptor type 2 (D2 DR ). Mutation screening of 223 additional patients (187 with ASD and 36 with ID ) identified a missense change of maternal origin disrupting CADPS 2/D2 DR interaction. CADPS 2 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 CADPS 2 is subjected to tissue‐ and temporal‐specific regulation in human and mice. We suggest that CADPS 2 variants may contribute to ID / ASD development, possibly through a parent‐of‐origin effect.