M170. GENETIC CHARACTERIZATION OF A COHORT OF PATIENTS AFFECTED BY SCHIZOPHRENIA. THE ROLE FOR RARE STRUCTURAL VARIANTS IN MODULATING TREATMENT RESISTANT ENDOPHENOTYPES: PRELIMINARY DATA

• Published in: Schizophrenia bulletin 2020-05, Vol.46 (Supplement_1), p.S201-S201
• Main Authors: Barone, Annarita, Iasevoli, Felice, Matrone, Marta, Filomena Buonaguro, Elisabetta, Falco, Mariateresa, Genesio, Rita, Pignataro, Piero, Capasso, Mario, Gambale, Antonella, Avagliano, Camilla, Razzino, Eugenio, Notar Francesco, Danilo, Ciccarelli, Mariateresa, Vitiello, Giuseppina, Andolfo, Immacolata, Nitsch, Lucio, Iolascon, Achille, de Bartolomeis, Andrea
• Format: Article
• Language: English
• Subjects: Poster Session II
• ISSN: 0586-7614; 1745-1701
• DOI: 10.1093/schbul/sbaa030.482

Abstract Background Schizophrenia (SCZ) is a debilitating mental illness characterized by a highly complex, heterogeneous, non-mendelian genetic background. Recent progress in dissecting genetic architecture of SCZ has accelerated over the last decade due to new advanced technologies. Genome-Wide Association Studies (GWAS) on extremely large samples of patients identified and replicated hundreds of Single-Nucleotide Polymorphism (SNPs), each exhibiting only a modest effect. The analysis of genomic Copy Number Variations (CNVs) clarified the role of rare structural variants conferring significant risk by disrupting multiple genes involved in neurodevelopmental pathways, and linked to SCZ. In this scenario, the aim of our study is to carry out a genetic characterization of a cohort of patients affected by SCZ, in order to assess the risk of recurrence, to elucidate putative pathogenetic mechanisms and, whenever possible, to conceive tailored interventions and therapies. Methods 34 patients (8 women and 26 men) affected by SCZ and admitted to Day Hospital at Psychiatric Division for Treatment Resistant Psychosis of the University of Naples Federico II were recruited, and underwent: i) psychopathological evaluation and assessment of clinical response to antipsychotics; ii) genetic counseling; iii) further diagnostic investigation by using Comparative Genomic Hybridization (CGH) + Single Nucleotide Polymorphism (SNP) microarray with 2x400k Agilent’s platform “GenetiSure” for detecting unbalanced chromosomal abnormalities and regions of homozygosity (ROHs). Results Structural pathogenetic rearrangements resulted in 9 (27%) patients. Those identified were the following: 15q13.3 deletion, 16p13.11 duplication, 22q11.22 deletion (TOP3B), 22q11.22 (PRODH, DGCR5, DGCR6), RBFOX1 deletion, TCF4 deletion, derivative X chromosome (X;Y translocation). Potentially pathogenic rearrangements, involving genes associated with psychiatric disorders or implicated in neurodevelopment, resulted in 15 patients (44%). No relevant CNVs were detected in 10 patients (29%), although they showed the presence of ROHs that may contain susceptibility loci, since many neurodevelopmental genes map onto or near these specific regions. Certain of these rearrangements occur in many patients, and certain patients showed likewise multiple rearrangements. Discussion The analysis of CNVs and SNPs allowed us to characterize the genetic disease structure in the whole cohort of patients and helped to r