POGZ de novo missense variants in neuropsychiatric disorders.

Background: De novo likely gene-disrupting variants of POGZ cause autism spectrum disorder (ASD) and intellectual disability. However, de novo missense variants of this gene were not well explored in neuropsychiatric disorders.

Methods: The single-molecule molecular inversion probes-based targeted sequencing method was performed on the proband. Variant was validated using Sanger sequencing in both proband and parents. Immunoblot analysis was performed to examine the expression of POGZ in patient-derived peripheral blood lymphocytes. Published POGZ de novo missense variants in neuropsychiatric disorders were reviewed.

Results: We detected a novel de novo missense variant in POGZ (c.1534C>A, p.H512N, NM_015100.4) in an individual with ASD. Immunoblot analysis revealed a dramatic reduction in POGZ protein in patient-derived peripheral blood lymphocytes suggesting a loss-of-function mechanism of this de novo missense variant. In addition, we collected and annotated additional eight POGZ de novo missense variants identified in neuropsychiatric disorders from literatures.

Conclusion: Our findings will be beneficial to the functional analysis of POGZ in ASD pathogenesis, and for genetic counseling and clinical diagnosis of patients with POGZ de novo missense variants.