Mosaic variegated aneuploidy syndrome with tetraploid, and predisposition to male infertility triggered by mutant CEP192

Jihong Guo; Wen-Bin He; Lei Dai; Fen Tian; Zhenqing Luo; Fang Shen; Ming Tu; Yu Zheng; Liu Zhao; Chen Tan; Yongteng Guo; Lan-Lan Meng; Wei Liu; Mei Deng; Xinghan Wu; Yu Peng; Shuju Zhang; Guang-Xiu Lu; Ge Lin; Hua Wang; Yue-Qiu Tan; Yongjia Yang

HGG Advances (Jan 2024)

Mosaic variegated aneuploidy syndrome with tetraploid, and predisposition to male infertility triggered by mutant CEP192

Jihong Guo,
Wen-Bin He,
Lei Dai,
Fen Tian,
Zhenqing Luo,
Fang Shen,
Ming Tu,
Yu Zheng,
Liu Zhao,
Chen Tan,
Yongteng Guo,
Lan-Lan Meng,
Wei Liu,
Mei Deng,
Xinghan Wu,
Yu Peng,
Shuju Zhang,
Guang-Xiu Lu,
Ge Lin,
Hua Wang,
Yue-Qiu Tan,
Yongjia Yang

Affiliations

Jihong Guo: Department of Medical Genetics, Hunan Children’s Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
Wen-Bin He: Hunan Guangxiu Hospital, Hunan Normal University School of Medicine, Changsha, China; Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China
Lei Dai: Department of Obstetrics, Xiangya Hospital of Central South University, Changsha, China
Fen Tian: Department of Medical Genetics, Hunan Children’s Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
Zhenqing Luo: Department of Medical Genetics, Hunan Children’s Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
Fang Shen: Department of Medical Genetics, Hunan Children’s Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
Ming Tu: Department of Medical Genetics, Hunan Children’s Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
Yu Zheng: Department of Medical Genetics, Hunan Children’s Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
Liu Zhao: Department of Medical Genetics, Hunan Children’s Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
Chen Tan: Hunan Guangxiu Hospital, Hunan Normal University School of Medicine, Changsha, China; Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China
Yongteng Guo: Hunan Guangxiu Hospital, Hunan Normal University School of Medicine, Changsha, China; Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China
Lan-Lan Meng: Hunan Guangxiu Hospital, Hunan Normal University School of Medicine, Changsha, China; Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China
Wei Liu: Department of Medical Genetics, Hunan Children’s Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
Mei Deng: Department of Medical Genetics, Hunan Children’s Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
Xinghan Wu: Department of Medical Genetics, Hunan Children’s Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
Yu Peng: Department of Medical Genetics, Hunan Children’s Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
Shuju Zhang: Department of Medical Genetics, Hunan Children’s Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
Guang-Xiu Lu: Hunan Guangxiu Hospital, Hunan Normal University School of Medicine, Changsha, China; Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China
Ge Lin: Hunan Guangxiu Hospital, Hunan Normal University School of Medicine, Changsha, China; Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China
Hua Wang: Department of Medical Genetics, Hunan Children’s Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China
Yue-Qiu Tan: Hunan Guangxiu Hospital, Hunan Normal University School of Medicine, Changsha, China; Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China; Corresponding author
Yongjia Yang: Department of Medical Genetics, Hunan Children’s Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China; Corresponding author

Journal volume & issue: Vol. 5, no. 1
p. 100256

Abstract

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Summary: In this study, we report on mosaic variegated aneuploidy (MVA) syndrome with tetraploidy and predisposition to infertility in a family. Sequencing analysis identified that the CEP192 biallelic variants (c.1912C>T, p.His638Tyr and c.5750A>G, p.Asn1917Ser) segregated with microcephaly, short stature, limb-extremity dysplasia, and reduced testicular size, while CEP192 monoallelic variants segregated with infertility and/or reduced testicular size in the family. In 1,264 unrelated patients, variant screening for CEP192 identified a same variant (c.5750A>G, p.Asn1917Ser) and other variants significantly associated with infertility. Two lines of Cep192 mice model that are equivalent to human variants were generated. Embryos with Cep192 biallelic variants arrested at E7 because of cell apoptosis mediated by MVA/tetraploidy cell acumination. Mice with heterozygous variants replicated the predisposition to male infertility. Mouse primary embryonic fibroblasts with Cep192 biallelic variants cultured in vitro showed abnormal morphology, mitotic arresting, and disruption of spindle formation. In patient epithelial cells with biallelic variants cultured in vitro, the number of cells arrested during the prophase increased because of the failure of spindle formation. Accordingly, we present mutant CEP192, which is a link for the MVA syndrome with tetraploidy and the predisposition to male infertility.

Published in HGG Advances

ISSN: 2666-2477 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Biology (General): Genetics
Website: https://www.cell.com/hgg-advances/home

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