Faying Liu, Lifeng Tian, Jun Tan, Zengming Li, Haiyan Qin, Dingfei Xu, Zhihui Huang, Xingwu Wu, Ge Chen, Qiongfang Wu, Yang Zou
{"title":"中国PCOS女性雌激素不敏感患者体外受精治疗中ESR1突变的鉴定","authors":"Faying Liu, Lifeng Tian, Jun Tan, Zengming Li, Haiyan Qin, Dingfei Xu, Zhihui Huang, Xingwu Wu, Ge Chen, Qiongfang Wu, Yang Zou","doi":"10.1186/s12958-022-01029-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a complex reproductive disorder, that affects approximately 5-10% of women of reproductive age. The disease is complex because its evolution may be impacted by genetic, lifestyle and environmental factors. Previous studies have emphasized the important roles of estrogen receptors in the pathogenesis of PCOS.</p><p><strong>Objective: </strong>To use whole exome sequencing (WES) to assess possible pathogenic factors in a PCOS patient who exhibited estrogen insensitivity during hormone replacement therapy (HRT) treatment.</p><p><strong>Methods: </strong>Genome sequencing and variant filtering via WES were performed in a patient with PCOS. DNA extraction from 364 unrelated female controls without PCOS was followed by PCR amplification, Sanger sequencing and sequence alignment. Evolutionary conservation analysis, protein structural modelling and in silico prediction were applied to analyse the potential pathogenicity of the novel ESR1 mutation.</p><p><strong>Result(s): </strong>During the controlled ovarian hyperstimulation (COH) period of an IVF cycle, the patient experienced markedly prolonged ovarian stimulation due to a poor response to gonadotropins (Gn) and elevated serum FSH. A novel heterozygous ESR1 mutation, c.619G > A/p.A207T, leading to the replacement of a highly conserved alanine with a threonine, was identified in this patient, via WES analysis. This novel variant was not identified in 364 unrelated female controls without PCOS, or in the Exome Aggregation Consortium (ExAC) or 1000 Genome Project.</p><p><strong>Conclusion(s): </strong>We identified a novel heterozygous ESR1 mutation in a Han Chinese PCOS woman exhibiting clinical signs of estrogen insensitivity. This study may provide new strategies for IVF therapy, especially for patients who exhibit estrogen insensitivity during IVF cycle.</p>","PeriodicalId":520764,"journal":{"name":"Reproductive biology and endocrinology : RB&E","volume":" ","pages":"157"},"PeriodicalIF":0.0000,"publicationDate":"2022-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9673392/pdf/","citationCount":"1","resultStr":"{\"title\":\"Identification of a novel ESR1 mutation in a Chinese PCOS woman with estrogen insensitivity in IVF treatment.\",\"authors\":\"Faying Liu, Lifeng Tian, Jun Tan, Zengming Li, Haiyan Qin, Dingfei Xu, Zhihui Huang, Xingwu Wu, Ge Chen, Qiongfang Wu, Yang Zou\",\"doi\":\"10.1186/s12958-022-01029-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a complex reproductive disorder, that affects approximately 5-10% of women of reproductive age. The disease is complex because its evolution may be impacted by genetic, lifestyle and environmental factors. Previous studies have emphasized the important roles of estrogen receptors in the pathogenesis of PCOS.</p><p><strong>Objective: </strong>To use whole exome sequencing (WES) to assess possible pathogenic factors in a PCOS patient who exhibited estrogen insensitivity during hormone replacement therapy (HRT) treatment.</p><p><strong>Methods: </strong>Genome sequencing and variant filtering via WES were performed in a patient with PCOS. DNA extraction from 364 unrelated female controls without PCOS was followed by PCR amplification, Sanger sequencing and sequence alignment. Evolutionary conservation analysis, protein structural modelling and in silico prediction were applied to analyse the potential pathogenicity of the novel ESR1 mutation.</p><p><strong>Result(s): </strong>During the controlled ovarian hyperstimulation (COH) period of an IVF cycle, the patient experienced markedly prolonged ovarian stimulation due to a poor response to gonadotropins (Gn) and elevated serum FSH. A novel heterozygous ESR1 mutation, c.619G > A/p.A207T, leading to the replacement of a highly conserved alanine with a threonine, was identified in this patient, via WES analysis. This novel variant was not identified in 364 unrelated female controls without PCOS, or in the Exome Aggregation Consortium (ExAC) or 1000 Genome Project.</p><p><strong>Conclusion(s): </strong>We identified a novel heterozygous ESR1 mutation in a Han Chinese PCOS woman exhibiting clinical signs of estrogen insensitivity. This study may provide new strategies for IVF therapy, especially for patients who exhibit estrogen insensitivity during IVF cycle.</p>\",\"PeriodicalId\":520764,\"journal\":{\"name\":\"Reproductive biology and endocrinology : RB&E\",\"volume\":\" \",\"pages\":\"157\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-11-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9673392/pdf/\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Reproductive biology and endocrinology : RB&E\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12958-022-01029-7\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive biology and endocrinology : RB&E","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12958-022-01029-7","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Identification of a novel ESR1 mutation in a Chinese PCOS woman with estrogen insensitivity in IVF treatment.
Background: Polycystic ovary syndrome (PCOS) is a complex reproductive disorder, that affects approximately 5-10% of women of reproductive age. The disease is complex because its evolution may be impacted by genetic, lifestyle and environmental factors. Previous studies have emphasized the important roles of estrogen receptors in the pathogenesis of PCOS.
Objective: To use whole exome sequencing (WES) to assess possible pathogenic factors in a PCOS patient who exhibited estrogen insensitivity during hormone replacement therapy (HRT) treatment.
Methods: Genome sequencing and variant filtering via WES were performed in a patient with PCOS. DNA extraction from 364 unrelated female controls without PCOS was followed by PCR amplification, Sanger sequencing and sequence alignment. Evolutionary conservation analysis, protein structural modelling and in silico prediction were applied to analyse the potential pathogenicity of the novel ESR1 mutation.
Result(s): During the controlled ovarian hyperstimulation (COH) period of an IVF cycle, the patient experienced markedly prolonged ovarian stimulation due to a poor response to gonadotropins (Gn) and elevated serum FSH. A novel heterozygous ESR1 mutation, c.619G > A/p.A207T, leading to the replacement of a highly conserved alanine with a threonine, was identified in this patient, via WES analysis. This novel variant was not identified in 364 unrelated female controls without PCOS, or in the Exome Aggregation Consortium (ExAC) or 1000 Genome Project.
Conclusion(s): We identified a novel heterozygous ESR1 mutation in a Han Chinese PCOS woman exhibiting clinical signs of estrogen insensitivity. This study may provide new strategies for IVF therapy, especially for patients who exhibit estrogen insensitivity during IVF cycle.