Identification of novel variants and candidate genes in women with 46,XX complete gonadal dysgenesis.

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Leilei Ding, Shan Deng, Pan Zhang, Duoduo Zhang, Qinjie Tian
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引用次数: 0

Abstract

Background: 46,XX complete gonadal dysgenesis (46,XX-CGD) is a rare disorder of sexual development (DSD) characterized by primary amenorrhea and a lack of spontaneous pubertal development in individuals with a 46,XX karyotype despite the presence of female internal and external genitalia due to failure of bilateral ovarian development. The condition is genetically heterogeneous, and in most cases, its etiology is unknown. Determining the genetic cause would provide insights into potential targets for genetic diagnosis and counseling.

Methods: To clarify the molecular mechanisms of 46,XX complete gonadal dysgenesis in the population of China, whole-exome sequencing (WES) was performed on DNA samples from patients with 46,XX-CGD. In silico analysis was conducted to predict the pathogenicity of the variants.

Results: We recruited 20 patients with 46,XX-CGD and identified 8 variants in 6 genes, including three homozygous variants in MCM9, POF1B, and PSMC3IP; compound heterozygous variants in TWNK; and three heterozygous variants in TP63 and INSRR, from 7 patients. These variants included 3 recurrent variants and 5 novel variants.

Conclusions: This study identified several novel variants, broadening the variant spectrum of 46,XX-CGD. 46,XX-CGD is a genetically heterogeneous condition, and WES is a powerful tool for determining its genetic etiology. The results of this study will aid researchers and clinicians in genetic counseling and suggest that WES is valuable for detecting 46,XX-CGD, which may lead to early interventions for patients.

鉴定 46,XX 完全性性腺发育不良女性的新型变体和候选基因。
背景:46,XX完全性性腺发育不良(46,XX-CGD)是一种罕见的性发育障碍(DSD),其特点是尽管双侧卵巢发育失败导致女性内外生殖器存在,但核型为46,XX的个体仍会出现原发性闭经和缺乏自发性青春期发育。这种疾病在遗传学上具有异质性,大多数情况下病因不明。确定遗传原因将有助于了解遗传诊断和咨询的潜在目标:方法:为了明确中国人群中 46,XX 完全性性腺发育不良的分子机制,我们对 46,XX-CGD 患者的 DNA 样本进行了全外显子组测序(WES)。结果:我们招募了 20 名 46,XX-CGD 患者,从 7 名患者中发现了 6 个基因中的 8 个变异体,包括 MCM9、POF1B 和 PSMC3IP 中的 3 个同源杂合变异体;TWNK 中的复合杂合变异体;TP63 和 INSRR 中的 3 个杂合变异体。这些变异包括 3 个复发性变异和 5 个新型变异:这项研究发现了几个新变异,扩大了46,XX-CGD的变异谱。46,XX-CGD是一种遗传异质性疾病,WES是确定其遗传病因的有力工具。这项研究的结果将有助于研究人员和临床医生进行遗传咨询,并表明 WES 对检测 46,XX-CGD 很有价值,可对患者进行早期干预。
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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来源期刊
Reproductive Biology and Endocrinology
Reproductive Biology and Endocrinology 医学-内分泌学与代谢
CiteScore
7.90
自引率
2.30%
发文量
161
审稿时长
4-8 weeks
期刊介绍: Reproductive Biology and Endocrinology publishes and disseminates high-quality results from excellent research in the reproductive sciences. The journal publishes on topics covering gametogenesis, fertilization, early embryonic development, embryo-uterus interaction, reproductive development, pregnancy, uterine biology, endocrinology of reproduction, control of reproduction, reproductive immunology, neuroendocrinology, and veterinary and human reproductive medicine, including all vertebrate species.
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