Evidence map›Paper›PMID 41272256›Full record

ArticleJournal of assisted reproduction and genetics2026

Novel missense variants in COX15 cause oocyte degeneration and female infertility.

Ran Yu, Xuelin Zhang, Qian Dou, Chunyi Li, Zhiqi Ye, Fangzhou Xu, Chi Xiong, Biaobang Chen, Weijie Wang, Qiaoli Li and 3 more

Abstract read
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In one paragraph

Article in Journal of assisted reproduction and genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Ran YuInstitute of Pediatrics, Children's Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Xuelin ZhangInstitute of Pediatrics, Children's Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Qian DouReproductive Medical Center, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.
Chunyi LiShenyang Jinghua Hospital, Liaoning, 110059, China.
Zhiqi YeInstitute of Pediatrics, Children's Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Fangzhou XuInstitute of Pediatrics, Children's Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Chi XiongInstitute of Pediatrics, Children's Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Biaobang ChenNHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai, 200032, China.
Weijie WangInternational Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.
Qiaoli LiInstitute of Pediatrics, Children's Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Lei WangInstitute of Pediatrics, Children's Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Qing SangInstitute of Pediatrics, Children's Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China. sangqing@fudan.edu.cn.
Zhihua ZhangInstitute of Pediatrics, Children's Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China. zhihuazhang_@fudan.edu.cn.

Funding

National Key Research and Development Program of China 2024YFC2706600National Natural Science Foundation of China 32130029National Natural Science Foundation of China 82325021National Natural Science Foundation of China 82371662
6 · The paper itself

Abstract

purposeTo identify novel pathogenic genes and variants responsible for oocyte degeneration and death.

methodsWhole-exome sequencing was conducted in 78 individuals with primary infertility characterized with oocyte degeneration and death, followed by Sanger sequencing of candidate variants. Pathogenicity of identified COX15 variants was characterized through morphological assessment, AlphaFold3-based structural modeling and functional validation including Western blotting and immunofluorescence.

resultsWe identified a compound-heterozygous COX15 variants and a homozygous COX15 variant in two affected individuals with oocyte degeneration. The variants c.C664T [p.R222C] was a previously reported recurrent pathogenic variant. The clinical records showed that majority of oocytes retrieved from affected individuals were immature and degenerated. Structural modeling assay showed that all the COX15 variants affected the binding pocket with heme o. The compound-heterozygous COX15 variants c.C905T [p.P302L] and c.C664T [p.R222C] in family 1 significantly decreased COX15 protein level in HeLa cells. While the homozygous variant c.C647T [p.P216L] decreased the COX1 protein level in oocytes from family 2 (II-1), implying the disruption of respiratory complex IV (COXIV) assembly.

conclusionsOur study identified two novel variants in COX15, and functional analysis confirmed the pathogenicity of the variants. Our findings expand the mutational spectrum of COX15 and making it a potential genetic diagnostic marker for those suffering from female infertility causing by oocyte degeneration.

Indexed as

Infertility, FemaleMutation, MissenseOocytesAdultExome SequencingFemaleHeLa CellsHumansPedigreeCOX15Female infertilityOocyte degenerationOocyte qualityVariant

Identifiers

PMID41272256
PMCPMC12901784

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