Dissecting Molecular Genetic Mechanisms of 1q21.1 CNV in Neuropsychiatric Disorders

Pathogenic copy number variations (CNVs) contribute to the etiology of neurodevelopmental/neuropsychiatric disorders (NDs). Increased CNV burden has been found to be critically involved in NDs compared with controls in clinical studies. The 1q21.1 CNVs, rare and large chromosomal microduplications and microdeletions, are detected in many patients with NDs. Phenotypes of duplication and deletion appear at the two ends of the spectrum. Microdeletions are predominant in individuals with schizophrenia (SCZ) and microcephaly, whereas microduplications are predominant in individuals with autism spectrum disorder (ASD) and macrocephaly. However, its complexity hinders the discovery of molecular pathways and phenotypic networks. In this review, we summarize the recent genome-wide association studies (GWASs) that have identified candidate genes positively correlated with 1q21.1 CNVs, which are likely to contribute to abnormal phenotypes in carriers. We discuss the clinical data implicated in the 1q21.1 genetic structure that is strongly associated with neurodevelopmental dysfunctions like cognitive impairment and reduced synaptic plasticity. We further present variations reported in the phenotypic severity, genomic penetrance and inheritance.

Automated summary

Pathogenic copy number variations (CNVs) play a crucial role in neurodevelopmental/neuropsychiatric disorders (NDs), with the 1q21.1 CNVs showing specific associations with different phenotypes. The genetic structure associated with 1q21.1 is strongly linked to neurodevelopmental dysfunctions like cognitive impairment and reduced synaptic plasticity, posing challenges for the discovery of molecular pathways and phenotypic networks. Variations in phenotypic severity, genomic penetrance, and inheritance are also reported.