Center of Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
Mol Genet Genomic Med. 2019 Sep;7(9):e900. doi: 10.1002/mgg3.900. Epub 2019 Jul 25.
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.
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.
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.
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.
POGZ 的新生致病变异可能导致自闭症谱系障碍 (ASD) 和智力障碍。然而，该基因的新生错义变异在神经精神疾病中尚未得到充分研究。
对先证者进行基于单分子分子倒置探针的靶向测序方法。通过 Sanger 测序在先证者及其父母中验证了变体。进行免疫印迹分析以检查患者来源的外周血淋巴细胞中 POGZ 的表达。回顾了神经精神疾病中已发表的 POGZ 新生错义变异。
我们在一名 ASD 患者中检测到 POGZ 中的一个新的新生错义变异（c.1534C>A，p.H512N，NM_015100.4）。免疫印迹分析显示患者来源的外周血淋巴细胞中 POGZ 蛋白明显减少，提示该新生错义变异具有功能丧失机制。此外，我们从文献中收集并注释了另外 8 种在神经精神疾病中发现的 POGZ 新生错义变异。
我们的发现将有助于研究 POGZ 在 ASD 发病机制中的功能，以及对 POGZ 新生错义变异患者的遗传咨询和临床诊断。
