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Genetic Etiologic Analysis in 74 Chinese Han Women with Idiopathic Premature Ovarian Insufficiency by Combined Molecular Genetic Testing
  • +8
  • Jiandong Shen,
  • Dianyun Qu,
  • Yan Gao,
  • Fangxi Sun,
  • Jiazi Xie,
  • Xueping Sun,
  • Dao Wang,
  • Xiang Ma,
  • Yugui Cui,
  • Jiayin Liu,
  • Feiyang Diao
Jiandong Shen
Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital
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Dianyun Qu
Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital
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Yan Gao
Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital
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Fangxi Sun
Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital
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Jiazi Xie
Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital
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Xueping Sun
Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital
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Dao Wang
The First Affliated Hospital of Nanjing Medical University
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Xiang Ma
Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital
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Yugui Cui
Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital
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Jiayin Liu
The State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University
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Feiyang Diao
First Affiliated Hospital with Nanjing Medical University
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Abstract

Premature ovarian insufficiency (POI) refers to women premature amenorrhea before the age of 40, elevated levels of follicle stimulating hormone (FSH). In clinic, the etiology of POI remains unknown in most patients. In this study, seventy-four Chinese Han women with idiopathic POI were collected to analyze the genetic etiology. Triplet repeat-primed polymerase chain reaction (TP-PCR) was performed to screen the FMR1 (CGG)n premutation, and then 60 POI related genes were sequenced by targeted next generation sequencing (NGS) in POI patients with normal FMR1. One patient (1/74) with FMR1 premutation was identified. Targeted NGS revealed that 15.07% (11/73) patients had pathogenic or likely pathogenic variants of Mendelian genes (FOXL2, EIF2B2, CYP17A1, CLPP, MCM9, GDF9, MSH5, ERCC6, POLG). Ten novel variants in six Mendelian genes were identified, such as CLPP c.355A>C (p.I119L) and c.688A>C (p.M230L), MCM9 c.1157C>T (p.T386M) and c.1291A>G (p.M431V), GDF9 c. 238C>T (p.Q80X), MSH5 c.604G>C (p.G202R) and c.2063T>C (p.I688T), ERCC6 c.C1769C>T (p.P590L), POLG c.2832G>C (p.E944D) and c.2821A>G (p.I941V). This study enriched the variant spectrum of POI related genes and suggested targeted NGS was an efficient and optional further clinical test for POI patients without FMR1 premutation.

Peer review status:Published

04 Feb 2021Published in Journal of Assisted Reproduction and Genetics. 10.1007/s10815-021-02083-7