Rare NRXN1 promoter variants in patients with schizophrenia
Rare NRXN1 promoter variants in patients with schizophrenia
Copy number variants (CNVs) affecting the neurexin 1 (NRXN1) gene have been found in a subgroup of patients with schizophrenia (SZ). NRXN1 expression is complex, with multiple alternative splice forms generated from two major transcripts; NRXN1alpha and NRXN1beta. The majority of CNVs in SZ are deletions affecting the proximal NRXN1alpha exons and promoter region. Rare chromosomal events are useful in understanding the genetic basis of complex psychiatric disorders since affected genes become feasible targets to analyze for more subtle genetic alterations. As a first step towards this goal, we resequenced the NRXN1alpha promoter region in 170 patients with SZ and a similar number of controls. Two rare mutations were identified in the patient population. One previously unknown single nucleotide polymorphism (SNP) was found in controls. Bioinformatics analysis suggests that binding to several transcription factors may be affected by the minor alleles. The findings suggest that in addition to chromosomal alterations disrupting the NRXN1alpha promoter, rare point mutations in the region may also be involved in SZ pathogenesis.
- New York University United States
- Albert Einstein College of Medicine United States
Adult, Male, Binding Sites, Base Sequence, Cell Adhesion Molecules, Neuronal, Calcium-Binding Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Middle Aged, Polymorphism, Single Nucleotide, Schizophrenia, Humans, Point Mutation, Female, Promoter Regions, Genetic, Neural Cell Adhesion Molecules, Genetic Association Studies
Adult, Male, Binding Sites, Base Sequence, Cell Adhesion Molecules, Neuronal, Calcium-Binding Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Middle Aged, Polymorphism, Single Nucleotide, Schizophrenia, Humans, Point Mutation, Female, Promoter Regions, Genetic, Neural Cell Adhesion Molecules, Genetic Association Studies
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