Consanguineous Chinese Familial Study Reveals that a Gross Deletion that Includes the SYCE1 Gene Region Is Associated with Premature Ovarian Insufficiency

  • Jing Zhe
  • Desheng Ye
  • Xin Chen
  • Yudong Liu
  • Xingyu Zhou
  • Ying Li
  • Jun Zhang
  • Shiling ChenEmail author
Original Article


Premature ovarian insufficiency (POI) is a highly heterogeneous ovarian disorder. Genetic factors account for the cause of POI. We aimed to analyze the genetic alterations in two affected sisters diagnosed with POI and their parents from a highly consanguineous Chinese Han family. Whole-exome sequencing was performed, and bioinformatics analysis was used to determine the potential genetic cause of POI in this family. A SYCE1 deletion was verified by Sanger sequencing. A homozygous deletion in SYCE1 was harbored by the proband and her affected sister, whereas both parents had heterozygous deletions. There were distinct differences in the amino acid sequences between wild-type and SYCE1 deletion. Domain analysis and 3D structural analysis of the SYCE1 deletion was also performed to evaluate the potential impact and pathogenicity of POI. The SYCE1 domain structure was truncated. Additionally, the 3D structure showed that the SYCE1 deletion changed the shape of the protein compared with that of wild-type SYCE1. This study revealed a novel SYCE1 deletion. This SYCE1 deletion may be the cause of POI. Genetic counseling for POI is helpful for researchers and clinicians to identify the mode of genetic inheritance for SYCE1 deletion in POI pathology.


Premature ovarian insufficiency Whole-exome sequencing SYCE1 



We sincerely thank the affected patients and their parents for their participation in this study. We are also grateful to all the clinical investigators for collecting patient information. We acknowledge Zaiwei Zhou, PhD, and Wenping Qu for assisting with the bioinformatics analysis. We thank American Journal Experts for its linguistic assistance during the preparation of this manuscript. The work reported in this article was completed at the Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University.

Author Contribution

Jing Zhe conceived and designed the study, collected the data, performed the data analysis and interpretation, and drafted and revised the manuscript. Desheng Ye, Xin Chen, Yudong Liu, Xingyu Zhou, Ying Li, and Jun Zhang collected the data. Shiling Chen designed the study, revised the manuscript, and approved the final version for publication.

Funding Information

The author(s) disclose the receipt of the following financial support for the research, authorship, and/or publication of this article. This work was supported by grants from the National Key Research & Developmental Program of China (2017YFC1001103) and the Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education under grant LC2016ZD010.

Compliance with Ethical Standards

This study was approved by Medical Ethics Committee of Nanfang Hospital, Southern Medical University (NFEC-2017-197). Written informed consent was obtained from all participating individuals.

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Matzuk MM, Lamb DJ. Genetic dissection of mammalian fertility pathways. Nat Cell Biol. 2002;4(Suppl):s41–9.PubMedGoogle Scholar
  2. 2.
    Hull MG, Glazener CM, Kelly NJ, Conway DI, Foster PA, Hinton RA, et al. Population study of causes, treatment, and outcome of infertility. Br Med J (Clin Res Ed). 1985;291(6510):1693–7.CrossRefGoogle Scholar
  3. 3.
    Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol. 1986;67(4):604–6.PubMedGoogle Scholar
  4. 4.
    Webber L, Davies M, Anderson R, et al. ESHRE Guideline: management of women with premature ovarian insufficiency. Hum Reprod. 2016;31(5):926–37.CrossRefGoogle Scholar
  5. 5.
    Torgerson DJ, Thomas RE, Reid DM. Mothers and daughters menopausal ages: is there a link? Eur J Obstet Gynecol Reprod Biol. 1997;74(1):63–6.CrossRefGoogle Scholar
  6. 6.
    Qin Y, Jiao X, Simpson JL, Chen ZJ. Genetics of primary ovarian insufficiency: new developments and opportunities. Hum Reprod Update. 2015;21(6):787–808.CrossRefGoogle Scholar
  7. 7.
    Jiao X, Zhang H, Ke H, Zhang J, Cheng L, Liu Y, et al. Premature ovarian insufficiency: phenotypic characterization within different etiologies. J Clin Endocrinol Metab. 2017;102(7):2281–90.CrossRefGoogle Scholar
  8. 8.
    Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, et al. Exome sequencing identifies the cause of a Mendelian disorder. Nat Genet. 2010;42(1):30–5.CrossRefGoogle Scholar
  9. 9.
    Zech M, Boesch S, Jochim A, Weber S, Meindl T, Schormair B, et al. Clinical exome sequencing in early-onset generalized dystonia and large-scale resequencing follow-up. Mov Disord. 2017;32(4):549–59.CrossRefGoogle Scholar
  10. 10.
    Patiño LC, Beau I, Carlosama C, Buitrago JC, González R, Suárez CF, et al. New mutations in non-syndromic primary ovarian insufficiency patients identified via whole-exome sequencing. Hum Reprod. 2017;32(7):1512–20.CrossRefGoogle Scholar
  11. 11.
    Jiao X, Ke H, Qin Y, Chen ZJ. Molecular genetics of premature ovarian insufficiency. Trends Endocrinol Metab. 2018;29(11):795-807CrossRefGoogle Scholar
  12. 12.
    Laissue P. The molecular complexity of primary ovarian insufficiency aetiology and the use of massively parallel sequencing. Mol Cell Endocrinol. 2018;460:170–80.CrossRefGoogle Scholar
  13. 13.
    Caburet S, Arboleda VA, Llano E, Overbeek PA, Barbero JL, Oka K, et al. Mutant cohesin in premature ovarian failure. N Engl J Med. 2014;370(10):943–9.CrossRefGoogle Scholar
  14. 14.
    Robinson JT, Thorvaldsdottir H, Winckler W, et al. Integrative genomics viewer. Nat Biotechnol. 2011;29(1):24–6.CrossRefGoogle Scholar
  15. 15.
    Thorvaldsdottir H, Robinson JT, Mesirov JP. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform. 2013;14(2):178–92.CrossRefGoogle Scholar
  16. 16.
    AlAsiri S, Basit S, Wood-Trageser MA, Yatsenko SA, Jeffries EP, Surti U, et al. Exome sequencing reveals MCM8 mutation underlies ovarian failure and chromosomal instability. J Clin Invest. 2015;125(1):258–62.CrossRefGoogle Scholar
  17. 17.
    Tenenbaum-Rakover Y, Weinberg-Shukron A, Renbaum P, Lobel O, Eideh H, Gulsuner S, et al. Minichromosome maintenance complex component 8 (MCM8) gene mutations result in primary gonadal failure. J Med Genet. 2015;52(6):391–9.CrossRefGoogle Scholar
  18. 18.
    Wood-Trageser MA, Gurbuz F, Yatsenko SA, Jeffries EP, Kotan LD, Surti U, et al. MCM9 mutations are associated with ovarian failure, short stature, and chromosomal instability. Am J Hum Genet. 2014;95(6):754–62.CrossRefGoogle Scholar
  19. 19.
    Bolcun-Filas E, Hall E, Speed R, et al. Mutation of the mouse Syce1 gene disrupts synapsis and suggests a link between synaptonemal complex structural components and DNA repair. PLoS Genet. 2009;5(2):e1000393.CrossRefGoogle Scholar
  20. 20.
    Zheng P, Griswold MD, Hassold TJ, Hunt PA, Small CL, Ye P. Predicting meiotic pathways in human fetal oogenesis. Biol Reprod. 2010;82(3):543–51.CrossRefGoogle Scholar
  21. 21.
    McGuire MM, Bowden W, Engel NJ, Ahn HW, Kovanci E, Rajkovic A. Genomic analysis using high-resolution single-nucleotide polymorphism arrays reveals novel microdeletions associated with premature ovarian failure. Fertil Steril. 2011;95(5):1595–600.CrossRefGoogle Scholar

Copyright information

© Society for Reproductive Investigation 2020

Authors and Affiliations

  • Jing Zhe
    • 1
  • Desheng Ye
    • 1
  • Xin Chen
    • 1
  • Yudong Liu
    • 1
  • Xingyu Zhou
    • 1
  • Ying Li
    • 1
  • Jun Zhang
    • 1
  • Shiling Chen
    • 1
    Email author
  1. 1.Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang HospitalSouthern Medical UniversityGuangzhouPeople’s Republic of China

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