Identification of a novel ESR1 mutation in a Chinese PCOS woman with estrogen insensitivity in IVF treatment.

Faying Liu, Lifeng Tian, Jun Tan, Zengming Li, Haiyan Qin, Dingfei Xu, Zhihui Huang, Xingwu Wu, Ge Chen, Qiongfang Wu, Yang Zou
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引用次数: 1

Abstract

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.

Abstract Image

Abstract Image

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
背景:多囊卵巢综合征(PCOS)是一种复杂的生殖疾病,影响约5-10%的育龄妇女。这种疾病很复杂,因为它的演变可能受到遗传、生活方式和环境因素的影响。既往研究强调雌激素受体在多囊卵巢综合征发病中的重要作用。目的:利用全外显子组测序(WES)评估在激素替代治疗(HRT)期间出现雌激素不敏感的PCOS患者可能的致病因素。方法:对1例PCOS患者进行基因组测序和WES变异筛选。从364名无PCOS的女性对照中提取DNA,进行PCR扩增、Sanger测序和序列比对。结果:在试管婴儿周期控制性卵巢过度刺激(COH)期间,由于促性腺激素(Gn)反应差和血清FSH升高,患者卵巢刺激明显延长。一种新的杂合ESR1突变,c.619G > A/p。通过WES分析,在该患者中发现了导致高度保守的丙氨酸被苏氨酸取代的A207T。在364名没有PCOS的女性对照中,也没有在ExAC或1000基因组计划中发现这种新的变异。结论:我们在一名表现出雌激素不敏感临床症状的中国汉族PCOS女性中发现了一种新的杂合ESR1突变。本研究可能为体外受精治疗提供新的策略,特别是对体外受精周期中出现雌激素不敏感的患者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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