Whole-exome sequencing in patients with premature ovarian insufficiency: early detection and early intervention

Hongli Liu,Yanwei Sha,Haijie Gao,Yanlong Wang,Wensheng Liu,Yaling Tang,Youzhu Li,Zhiying Su,Jin Lin,Xiaoli Wei,Yifeng Wang

doi:10.1186/s13048-020-00716-6

Abstract

BackgroundThe loss of ovarian function in women, referred to as premature ovarian insufficiency (POI), is associated with a series of concomitant diseases. POI is genetically heterogeneous, and in most cases, the etiology is unknown.MethodsWhole-exome sequencing (WES) was performed on DNA samples obtained from patients with POI, and Sanger sequencing was used to validate the detected potentially pathogenic variants. An in silico analysis was carried out to predict the pathogenicity of the variants.ResultsWe recruited 24 patients with POI and identified variants in POI-related genes in 14 patients, including bi-allelic mutations in DNAH6, HFM1, EIF2B2, BNC, and LRPPRC and heterozygous variants in BNC1, EIF2B4, FOXL2, MCM9, FANCA, ATM, EIF2B3, and GHR. No variants in the above genes were detected in the WES data obtained from 29 women in a control group without POI. Determining a clear genetic etiology could significantly increase patient compliance with appropriate intervention strategies.ConclusionsOur study confirmed that POI is a genetically heterogeneous condition and that whole-exome sequencing is a powerful tool for determining its genetic etiology. The results of this study will aid researchers and clinicians in genetic counseling and suggests the potential of WES for the detection of POI and thus early interventions for patients with POI.

Highlights

The loss of ovarian function in women, referred to as premature ovarian insufficiency (POI), is associated with a series of concomitant diseases
With the significant decrease in the price of Whole-exome sequencing (WES), it has emerged as a powerful tool with potential for clinical applications in the early detection of POI and timely intervention for patients with POI
Clinical features of patients with POI All 24 patients were diagnosed with sporadic POI according to standard criteria

Summary

Introduction

The loss of ovarian function in women, referred to as premature ovarian insufficiency (POI), is associated with a series of concomitant diseases. POI is genetically heterogeneous, and in most cases, the etiology is unknown. Premature ovarian insufficiency (POI) is defined as amenorrhea before the age of 40 and is characterized by FSH levels greater than 25 IU/L in two measurements for at least 4 weeks [1]. Genetic defects are a common cause of POI, as has been proven in a large number of studies. Whole-exome sequencing (WES) is widely used to identify the genetic etiologies of various diseases [7]. Gynecologists diagnose and treat POI only based on a patient’s symptoms, and genetic methods have not been widely used to identify the genetic causative factors of idiopathic POI. A clear genetic etiology could significantly improve treatment compliance

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Discussion

Conclusion