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

CEP192 mutation male infertility mosaic variegated aneuploidy tetraploidy

Journal

HGG advances
ISSN: 2666-2477
Titre abrégé: HGG Adv
Pays: United States
ID NLM: 101772885

Informations de publication

Date de publication:
19 Nov 2023
Historique:
received: 03 08 2023
revised: 15 11 2023
accepted: 15 11 2023
pubmed: 20 11 2023
medline: 20 11 2023
entrez: 20 11 2023
Statut: aheadofprint

Résumé

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.

Identifiants

DOI: 10.1016/j.xhgg.2023.100256 PMID: 37981762
pubmed: 37981762
pii: S2666-2477(23)00088-X
doi: 10.1016/j.xhgg.2023.100256
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

100256

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Jihong Guo (J)

Department of Medical Genetics, Hunan Children's Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China.

Wen-Bin He (WB)

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 (L)

Department of Obstetrics, Xiangya Hospital of Central South University, Changsha, China.

Fen Tian (F)

Department of Medical Genetics, Hunan Children's Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China.

Zhenqing Luo (Z)

Department of Medical Genetics, Hunan Children's Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China.

Fang Shen (F)

Department of Medical Genetics, Hunan Children's Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China.

Ming Tu (M)

Department of Medical Genetics, Hunan Children's Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China.

Yu Zheng (Y)

Department of Medical Genetics, Hunan Children's Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China.

Liu Zhao (L)

Department of Medical Genetics, Hunan Children's Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China.

Chen Tan (C)

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 (Y)

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 (LL)

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 (W)

Department of Medical Genetics, Hunan Children's Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China.

Mei Deng (M)

Department of Medical Genetics, Hunan Children's Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China.

Xinghan Wu (X)

Department of Medical Genetics, Hunan Children's Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China.

Yu Peng (Y)

Department of Medical Genetics, Hunan Children's Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China.

Shuju Zhang (S)

Department of Medical Genetics, Hunan Children's Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China.

Guang-Xiu Lu (GX)

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 (G)

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 (H)

Department of Medical Genetics, Hunan Children's Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China.

Yue-Qiu Tan (YQ)

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. Electronic address: tanyueqiu@csu.edu.cn.

Yongjia Yang (Y)

Department of Medical Genetics, Hunan Children's Hospital, Xiangya Medical School & Reproductive Medicine Center, Xiangya Hospital, Central South University, Changsha, China. Electronic address: yongjia727@aliyun.com.

Classifications MeSH