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Clinical and genetic analysis of an isolated follicle-stimulating hormone deficiency female patient

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Objective

To characterize the clinical features of a female patient with isolated follicle-stimulating hormone (FSH) deficiency and to investigate the underlying mechanisms of FSH inactivation.

Methods

The proband was a 29-year-old woman with primary amenorrhea, impaired pubertal development, and infertility. Subsequently, reproductive endocrine was screened. DNA sequencing was conducted for the identification of FSHβ mutation. RT-PCR, western blots, in vitro immunometric assay, and bioassay were performed to confirm the impact of the mutation on FSH expression and biological activity. Molecular model consisting of FSHα and mutant FSHβ subunit was built for the structural analysis of FSH protein.

Results

The evaluation of reproductive endocrine revealed undetectable basal and GnRH-stimulated serum FSH. Sequencing of the FSHβ gene identified a homozygous nonsense mutation at codon 97 (Arg97X). RT-PCR and western blot analysis revealed the mutation Arg97X did not affect FSHβ mRNA and protein expression. But in vitro immunometric assay and bioassay demonstrated the production of normal bioactive FSH protein was disturbed by the mutation Arg97X. Structural analysis showed the surface structure of the resulting mutant FSH presented with lock-and-key, mosaic binding pattern, while the native structure was an encircling binding mode.

Conclusion

The mutation Arg97X could disturb structural stability of the resulting FSH protein consisting of FSHα and mutant FSHβ subunit, which may lead to FSH deficiency.

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Funding

This work was supported by the research grants from:

1. National Key Research and Development Program (China, 2018YFC1002103)

2. The Chinese Medical Association (16020520668)

3. The Natural Science Foundation of Hubei Province (China, 2017CFB752)

Author information

Author notes

  1. Lixia Zhu, Nan Xiao and Tao Zhang contributed equally to this work.

Authors and Affiliations

  1. Reproductive Medicine Center, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, People’s Republic of China

    Lixia Zhu, Tao Zhang, Bei Xu, Zishui Fang & Lei Jin

  2. Department of Center for Reproductive Medicine, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, 300100, People’s Republic of China

    Nan Xiao

  3. The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China

    Pingping Kong

Authors
  1. Lixia Zhu
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  2. Nan Xiao
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  3. Tao Zhang
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  4. Pingping Kong
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  5. Bei Xu
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  6. Zishui Fang
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  7. Lei Jin
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Corresponding author

Correspondence to Lei Jin.

Ethics declarations

Before the uFSH treatment, the study protocol was approved by the Medical Ethics Committee of Tongji Hospital and written informed consents were obtained from the patient. Researches were conducted according to the Declaration of Helsinki for medical research.

Conflict of interest

The authors declare that they have no competing interests.

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Précis

Clinical and genetic analysis of an isolated follicle-stimulating hormone deficiency female patient.

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Zhu, L., Xiao, N., Zhang, T. et al. Clinical and genetic analysis of an isolated follicle-stimulating hormone deficiency female patient. J Assist Reprod Genet 37, 1441–1448 (2020). https://doi.org/10.1007/s10815-020-01786-7

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  • DOI: https://doi.org/10.1007/s10815-020-01786-7

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