Genetic etiologic analysis in 74 Chinese Han women with idiopathic premature ovarian insufficiency by combined molecular genetic testing

Abstract

Purpose

To identify the disease-causing genes of Chinese Han women with idiopathic premature ovarian insufficiency (POI).

Methods

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.

Results

A total of 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).

Conclusion

This study suggested targeted NGS was an efficient etiologic test for idiopathic POI patients without FMR1 premutation and enriched the variant spectrum of POI-related genes.

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Fig. 1
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Data availability

The data that supports the findings of this study are available in the supplementary material of this article.

Code availability

The version of each software applications was indicated in the text.

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Funding

This study was supported by the National Key Research and Development Program of China (2016YFC1000200, 2017YFC1001602) and the National Natural Science Foundation of China (81471429, 81730041) and Natural Science Foundation of Jiangsu Province (BK20201488).

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JS, JL, and FD conceived and designed the study. JS, YG, and XM collected samples. DY, FS, JX, and XS performed the experiments. JS, DW, and YC analyzed the data. JS wrote the manuscript. JL and FD revised the manuscript. All authors read and approved the manuscript.

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Correspondence to Jiayin Liu or Feiyang Diao.

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Shen, J., Qu, D., Gao, Y. et al. Genetic etiologic analysis in 74 Chinese Han women with idiopathic premature ovarian insufficiency by combined molecular genetic testing. J Assist Reprod Genet (2021). https://doi.org/10.1007/s10815-021-02083-7

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Keywords

  • Premature ovarian insufficiency
  • POI
  • Next-generation sequencing
  • NGS
  • Variant