机构：[1]Center of Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China[2]The First People's Hospital of Yunnan Province, Kunming, Yunnan, China云南省第一人民医院[3]National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China[4]Mental Health Center of Shandong Province, Jinan, Shandong, China[5]Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan, China[6]Hunan Key Laboratory of Animal Models for Human Diseases, Changsha, Hunan, China[7]Key Laboratory of Medical Information Research, Central South University, Changsha, Hunan, China[8]CAS Center for Excellence in Brain Science and Intelligences Technology (CEBSIT), Shanghai, China
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.
基金：
National Natural Science Foundation
of China, Grant/Award Number:
31671114,81871079, 81330027, 81525007,
81730036 and 81671122; the Young Talent
Lifts Project of CAST and the Innovation‐
Driven Project of Central South University,
Grant/Award Number: 2016CX038;
The Natural Science Foundation of
Hunan Province, Grant/Award Number:
2016RS2001, 2016JC2055; Central
South University; Key R&D program of
Hunan Province, Grant/Award Number:
2018DK2016
第一作者机构：[1]Center of Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China[2]The First People's Hospital of Yunnan Province, Kunming, Yunnan, China
共同第一作者：
通讯作者：
通讯机构：[1]Center of Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China[6]Hunan Key Laboratory of Animal Models for Human Diseases, Changsha, Hunan, China[7]Key Laboratory of Medical Information Research, Central South University, Changsha, Hunan, China[8]CAS Center for Excellence in Brain Science and Intelligences Technology (CEBSIT), Shanghai, China[*1]Center of Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
推荐引用方式(GB/T 7714)：
Zhao Wenjing,Quan Yingting,Wu Huidan,et al.POGZ de novo missense variants in neuropsychiatric disorders[J].MOLECULAR GENETICS & GENOMIC MEDICINE.2019,7(9):doi:10.1002/mgg3.900.
APA：
Zhao, Wenjing,Quan, Yingting,Wu, Huidan,Han, Lin,Bai, Ting...&Xia, Kun.(2019).POGZ de novo missense variants in neuropsychiatric disorders.MOLECULAR GENETICS & GENOMIC MEDICINE,7,(9)
MLA：
Zhao, Wenjing,et al."POGZ de novo missense variants in neuropsychiatric disorders".MOLECULAR GENETICS & GENOMIC MEDICINE 7..9(2019)
