Copy Number Variations and Schizophrenia

Abstract

Schizophrenia is a neurodevelopmental disorder with genetic and environmental factors involved in its aetiology. Genetic liability contributing to the development of schizophrenia is a subject of extensive research activity, as reliable data regarding its aetiology would enable the improvement of its therapy and the development of new methods of treatment. A multitude of studies in this field focus on genetic variants, such as copy number variations (CNVs) or single-nucleotide variants (SNVs). Certain genetic disorders caused by CNVs including 22q11.2 microdeletion syndrome, Burnside-Butler syndrome (15q11.2 BP1-BP2 microdeletion) or 1q21.1 microduplication/microdeletion syndrome are associated with a higher risk of developing schizophrenia. In this article, we provide a unifying framework linking these CNVs and their associated genetic disorders with schizophrenia and its various neural and behavioural abnormalities.

Late onset psychosis in a case of 15q11.2 BP1-BP2 microdeletion (Burnside–Butler) syndrome: A case report and literature review

“…Numerous studies have established significant associations between microdeletion and conditions such as schizophrenia and related psychoses. 1 , 3 , 9 , 13 – 17 This is supported by the observation that people with learning disabilities and schizophrenia had a higher prevalence of the 15q11.2 deletion than the general population. 13 In schizophrenia patients, the prevalence of the 15q11.2 BP1-BP2 deletion ranges from 0.14% to 0.65%.…”

“…Davis et al 3 identified variations in BBS clinical presentations depending on the deletion origin (maternal or paternal). Maternal origin deletions are associated with a higher risk of developmental, motor, and speech delays, intellectual and learning problems, autism, and behavioral/psychiatric diagnoses.…”

“…PWS involves deletions of the paternal chromosome 15q11-q13 region and is associated with more severe clinical impairments, whereas AS involves deletions of the maternal chromosome 15q11-q13 region. 2 , 3 Individuals with PWS and larger type I deletions exhibit more severe clinical impairments than those with deletions specifically in the 15q11.2 BP1-BP2 region, as observed in individuals with BBS.…”

“…BBS, being an autosomal dominant genetic disorder with incomplete penetrance, presents varied expression among people with this syndrome. 1 , 3 Hence, not all individuals with microdeletions within the 15q11.2 band are clinically affected and may not exhibit the same symptoms and features. This case report highlights an unusual instance of late-onset psychosis in a patient with BBS and emphasizes the importance of comprehensive psychiatric evaluations for such individuals.…”

Clozapine Use in 22q11.2 Deletion Syndrome

“…1 The syndrome also confers significant risk for the development of schizophrenia, such that approximately 25% of individuals develop a psychotic illness. 2 Moreover, while numerous other deletion and duplication syndromes also confer risk for psychosis, 3 22q11.2 deletions represent the most common clinically relevant copy number variation in schizophrenia, and a variety of clinical, cognitive, and biomarker abnormalities are associated with the development of psychotic symptoms in individuals with this disorder. 2 Recommendations regarding the management of psychotic symptoms in 22q11.2 deletion syndrome are in keeping with treatment guidelines for individuals with schizophrenia in general.…”