TY - THES ID - 136784952 TI - The neurexin/neuroligin pathway genes in psychiatric disorders: literature overview and copy number variation analysis in adults with intellectual disability. AU - Populaire, Pieter AU - Vogels, Annick AU - Van Buggenhout, Griet AU - KU Leuven. Faculteit Geneeskunde. Opleiding Master in de geneeskunde (Leuven) PY - 2019 PB - Leuven KU Leuven. Faculteit Geneeskunde DB - UniCat UR - https://www.unicat.be/uniCat?func=search&query=sysid:136784952 AB - Background: In the past decade, there has been a major progress in the understanding of the complex genetic architecture of psychiatric disorders. This study focusses on the neurexin/neuroligin pathway. We provide an overview of literature on this pathway and its clinical relevance. In a selected population of adults with dual diagnosis of intellectual disability and psychiatric disorders, we investigate the role of copy number variations (CNVs) involving genes of interest in this pathway. Materials and methods: CNV-analysis was performed in 283 adult patients with dual diagnosis of intellectual disability and psychiatric disorders. Adults with pathogenic or variant of unknown significance (VOUS) likely pathogenic CNVs were included. In the next step, CNVs containing at least one gene of the neurexin/neuroligin pathway were selected. The psychiatric phenotype was described and compared with data from literature. Results: We identified 3241 CNVs in 283 patients. 157 CNVs were labeled as pathogenic (23) and VOUS likely pathogenic (124). 12 of the selected CNVs contained a gene in the neurexin/neuroligin pathway. We excluded 1 CNV only involving a gene in the NMDA-sidetrack. CNVs involving APBA1, Homer1, Nrxn2 and Shank3 were present in 1 patient. CNVs involving APBA2, Nrxn1 or STX1A were detected in 2 patients. 1 patient contained a single CNV involving NLGN4X, NLGN3, CASK orr DLG3. We found clinical similarities in our sample having CNVs encompassing Neurexins, STX1A and Shank3 with phenotypes described in literature. Discussion: We described the neurexin/neuroligin pathway and its clinical importance for intellectual disability and psychiatric disorders. In a group patients with a dual diagnosis of intellectual disability and psychiatric disorders, 3.9% were found to have a CNV involving at least one of the genes of this pathway. Recurring diagnoses in our patient sample were autism spectrum disorder (ASD) and schizophrenia. This study proposes the role of the neurexin/neuroligin pathway in the genetic predisposition of ASD and schizophrenia in intellectually disabled persons. ER -