A rare deleterious missense mutation in the AXIN2 gene in Chinese women with polycystic ovary syndrome
Background Polycystic ovary syndrome (PCOS) is an endocrine disorders and characterized by polycystic ovary morphology and oligomenorrhea, affecting fertility and health condition of female around the world. The causative factors of PCOS are complex, and genetic structure remains a long-standing med...
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Taylor & Francis Group
2025-12-01
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| Series: | Gynecological Endocrinology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/09513590.2025.2463545 |
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| author | Ying Zhang Yu Chen Fa-Ying Liu Jing-Wen Fu Xian-Xian Liu Jun Tan Ou-Ping Huang Yang Zou |
| author_facet | Ying Zhang Yu Chen Fa-Ying Liu Jing-Wen Fu Xian-Xian Liu Jun Tan Ou-Ping Huang Yang Zou |
| author_sort | Ying Zhang |
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| description | Background Polycystic ovary syndrome (PCOS) is an endocrine disorders and characterized by polycystic ovary morphology and oligomenorrhea, affecting fertility and health condition of female around the world. The causative factors of PCOS are complex, and genetic structure remains a long-standing medical challenge in genetics. Previous genome-wide association study (GWAS) showed that Wing-less-related integration site (Wnt) signaling is the most affected pathway among PCOS-related risk genes, and genetic mutations in the Wnt/β-catenin signaling may lead to abnormal development of PCOS.Objective To explore the possibility of axis inhibitor-2 (AXIN2) variants in Chinese women with PCOS and assess their pathogenicities.Methods A total of 365 Chinese women with PCOS and 905 women without PCOS as control were recruited from Jiangxi Provincial Maternal and Child Health Hospital, All of the 11 exons and flanking regions of the AXIN2 gene were amplified by polymerase chain reaction (PCR), the potential variants were analyzed by Sanger sequencing. The evolutionary conservation analysis of the identified Axin-2 mutant was analyzed among 15 vertebrates from human to zebrafish. The protein structure change was analyzed between the wild-type and mutation-type. The pathogenicity of AXIN2 variant was further analyzed in silico.Results We totally identified 7 genetic variants of AXIN2 in this study, including 4 synonymous and 3 missense. Among them, we find a rare deleterious missense variant [p.R714W (c.2140C > T)]. The allele frequencies of this variant were 0.82% and 0.17% in PCOS cases and matched controls, respectively. And it was ranging from 7.89e-5 to 1.47e-4 in public databases. Fisher’s exact test indicated that the allele frequencies in PCOS were p < 0.05 compared to both the controls and the databases. Especially, the mutant amino acid site is highly conserved in vertebrates, while the mutation changed the 714th arginine to tryptophan resulting in significant change in the protein structural of Axin-2.Conclusion In this study, we identified a rare deleterious missense AXIN2 mutation [p.R714W (c.2140C > T)] in Chinese women with PCOS, and this mutant is probably pathogenic. This study may provide a new perspective on revealing the genetic variation of PCOS. |
| format | Article |
| id | doaj-art-b0b4005f6c5a4977bc0fc90d115f0272 |
| institution | Kabale University |
| issn | 0951-3590 1473-0766 |
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| publishDate | 2025-12-01 |
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| spelling | doaj-art-b0b4005f6c5a4977bc0fc90d115f02722025-02-06T14:34:59ZengTaylor & Francis GroupGynecological Endocrinology0951-35901473-07662025-12-0141110.1080/09513590.2025.2463545A rare deleterious missense mutation in the AXIN2 gene in Chinese women with polycystic ovary syndromeYing Zhang0Yu Chen1Fa-Ying Liu2Jing-Wen Fu3Xian-Xian Liu4Jun Tan5Ou-Ping Huang6Yang Zou7Key Laboratory of Women’s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaKey Laboratory of Women’s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaKey Laboratory of Women’s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaCollege of Food Science, South China Agricultural University, Guangzhou, ChinaKey Laboratory of Women’s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaKey Laboratory of Women’s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaKey Laboratory of Women’s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaKey Laboratory of Women’s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, ChinaBackground Polycystic ovary syndrome (PCOS) is an endocrine disorders and characterized by polycystic ovary morphology and oligomenorrhea, affecting fertility and health condition of female around the world. The causative factors of PCOS are complex, and genetic structure remains a long-standing medical challenge in genetics. Previous genome-wide association study (GWAS) showed that Wing-less-related integration site (Wnt) signaling is the most affected pathway among PCOS-related risk genes, and genetic mutations in the Wnt/β-catenin signaling may lead to abnormal development of PCOS.Objective To explore the possibility of axis inhibitor-2 (AXIN2) variants in Chinese women with PCOS and assess their pathogenicities.Methods A total of 365 Chinese women with PCOS and 905 women without PCOS as control were recruited from Jiangxi Provincial Maternal and Child Health Hospital, All of the 11 exons and flanking regions of the AXIN2 gene were amplified by polymerase chain reaction (PCR), the potential variants were analyzed by Sanger sequencing. The evolutionary conservation analysis of the identified Axin-2 mutant was analyzed among 15 vertebrates from human to zebrafish. The protein structure change was analyzed between the wild-type and mutation-type. The pathogenicity of AXIN2 variant was further analyzed in silico.Results We totally identified 7 genetic variants of AXIN2 in this study, including 4 synonymous and 3 missense. Among them, we find a rare deleterious missense variant [p.R714W (c.2140C > T)]. The allele frequencies of this variant were 0.82% and 0.17% in PCOS cases and matched controls, respectively. And it was ranging from 7.89e-5 to 1.47e-4 in public databases. Fisher’s exact test indicated that the allele frequencies in PCOS were p < 0.05 compared to both the controls and the databases. Especially, the mutant amino acid site is highly conserved in vertebrates, while the mutation changed the 714th arginine to tryptophan resulting in significant change in the protein structural of Axin-2.Conclusion In this study, we identified a rare deleterious missense AXIN2 mutation [p.R714W (c.2140C > T)] in Chinese women with PCOS, and this mutant is probably pathogenic. This study may provide a new perspective on revealing the genetic variation of PCOS.https://www.tandfonline.com/doi/10.1080/09513590.2025.2463545Polycystic ovary syndromeChinesemutationAXIN2Wnt/β-catenin signaling pathway |
| spellingShingle | Ying Zhang Yu Chen Fa-Ying Liu Jing-Wen Fu Xian-Xian Liu Jun Tan Ou-Ping Huang Yang Zou A rare deleterious missense mutation in the AXIN2 gene in Chinese women with polycystic ovary syndrome Gynecological Endocrinology Polycystic ovary syndrome Chinese mutation AXIN2 Wnt/β-catenin signaling pathway |
| title | A rare deleterious missense mutation in the AXIN2 gene in Chinese women with polycystic ovary syndrome |
| title_full | A rare deleterious missense mutation in the AXIN2 gene in Chinese women with polycystic ovary syndrome |
| title_fullStr | A rare deleterious missense mutation in the AXIN2 gene in Chinese women with polycystic ovary syndrome |
| title_full_unstemmed | A rare deleterious missense mutation in the AXIN2 gene in Chinese women with polycystic ovary syndrome |
| title_short | A rare deleterious missense mutation in the AXIN2 gene in Chinese women with polycystic ovary syndrome |
| title_sort | rare deleterious missense mutation in the axin2 gene in chinese women with polycystic ovary syndrome |
| topic | Polycystic ovary syndrome Chinese mutation AXIN2 Wnt/β-catenin signaling pathway |
| url | https://www.tandfonline.com/doi/10.1080/09513590.2025.2463545 |
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