Abstract
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.
Highlights
Rare copy number variations (CNVs), such as chromosomal deletions and duplications, have raised much scientific interest in etiological studies of neuropsychiatric disorders (NDs)
Among the aforementioned associated CNVs, this paper aimed to focus on the 1q21.1 CNV that is found with high incidence in autism spectrum disorder (ASD), SCZ, attention deficit hyperactivity disorder (ADHD), intellectual disability (ID) and epilepsy [16]
The neuroblastoma breakpoint family (NBPF) transcript level was significantly correlated with neuroblastoma susceptibility and it is highly expressed in the fetal brain, suggesting that the gene plays an important role in the developing brain [70]
Summary
Rare CNVs, such as chromosomal deletions and duplications, have raised much scientific interest in etiological studies of NDs. It has been suggested that genetics play a major role in NDs, with ~52.4% and ~80% of inheritability in ASD and SCZ, respectively. 40% of carriers had de novo mutations, and the majority of the de novo mutations (91%) were pathogenic [4] These patterns show up in most ND studies, including ASD, SCZ, intellectual disability (ID) and attention deficit hyperactivity disorder (ADHD) [5,6,7]. These findings shed light on the contribution of CNVs to the risks of different NDs
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