Establishment of a patient-derived induced pluripotent stem cells with 22q11.2 microdeletion: a model system for studying neurodevelopmental disorders

Abstract

Background: Neurodevelopmental disorders (NDDs), including autism spectrum disorders, intellectual disability and schizophrenia, represent a public health challenge in modern societies. However, molecular mechanisms underlying NDDs are still unknown. 22q11.2 Deletion Syndrome (22q11.2DS), caused by microdeletion 22q11.2, is one of the syndromes with a high risk for NDDs; it is one of the strongest known risk factors for development of psychiatric illness and one of the highest known genetic risks for schizophrenia. Material and Methods: Peripheral blood mononuclear cells from patients with 22q11.2DS and control subjects were reprogrammed using CytoTune™-iPS 2.0 Sendai Reprogramming Kit. Characterization of generated iPSC lines were done by analyzing their morphology, genomic integrity, pluripotency and the ability to differentiate into three germ layers. Results: Peripheral blood mononuclear cells from seven patients with 22q11.2 microdeletion and three healthy controls were reprogrammed. Genotyping revealed that some of the iPSC lines contain additional CNVs. All generated iPS cell lines express markers of pluripotency and have ability to differentiate into three germ layers. Conclusion: iPSC lines derived from patients with 22q11.2DS and healthy controls were successfully established. They represent a powerful model system for studying molecular mechanisms underlying NDDs.Book of absctracts: European Society of Human Genetics (ESHG) 2025 Conference, May 24–27, 2025. Milan, Ital