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Novel PMM2 missense mutation in a Chinese family with non-syndromic premature ovarian insufficiency

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

Abstract

Purpose

This study sought to identify a disease-related gene in a consanguineous Chinese family in which there were two premature ovarian insufficiency (POI) sisters.

Method

We used whole-exome sequencing and Sanger sequencing to identify the disease-causing gene. Results were verified using an assay of mutant protein and in silico analyses.

Result

We identified a novel missense mutation (NM_000303: c.556G>A, p.Gly186Arg) in the PMM2 gene. The two sisters suffer from premature ovarian insufficiency (POI) only and have no other symptoms of congenital disorder of glycosylation type-1a (CDG-Ia). We found that the enzymic activity of the mutant PMM2 protein was reduced by 55.21% (p < 0.05) when compared with wild type, and many in silico tools suggested the mutation is disease-related.

Conclusion

This particular gene modification results in changes in activity of phosphomannomutase modification, which could lead to PMM2-CDG-Ia with an uncommon phenotype.

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References

  1. Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol. 1986;67(4):604–6.

    CAS  PubMed  Google Scholar 

  2. Santoro N. Mechanisms of premature ovarian failure. Ann Endocrinol (Paris). 2003;64(2):87–92.

    CAS  Google Scholar 

  3. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 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.

    Article  PubMed  Google Scholar 

  5. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Qin Y, Guo T, Li G, Tang TS, Zhao S, Jiao X, et al. CSB-PGBD3 mutations cause premature ovarian failure. PLoS Genet. 2015;11(7):e1005419.

    Article  PubMed  PubMed Central  Google Scholar 

  7. He WB, Tu CF, Liu Q, Meng LL, Yuan SM, Luo AX, et al. DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing. J Med Genet. 2018;55(3):198–204.

    CAS  PubMed  Google Scholar 

  8. Kristiansson B, Stibler H, Wide L. Gonadal function and glycoprotein hormones in the carbohydrate-deficient glycoprotein (CDG) syndrome. Acta Paediatr. 1995;84(6):655–9.

    Article  CAS  PubMed  Google Scholar 

  9. Matthijs G, Schollen E, van Schaftingen E, Cassiman JJ, Jaeken J. Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1A. Am J Hum Genet. 1998;62(3):542–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Freeze HH. Genetic defects in the human glycome. Nat Rev Genet. 2006;7(7):537–51.

    Article  CAS  PubMed  Google Scholar 

  11. Grunewald S. The clinical spectrum of phosphomannomutase 2 deficiency (CDG-Ia). Biochim Biophys Acta. 2009;1792(9):827–34.

    Article  PubMed  Google Scholar 

  12. Kjaergaard S, Skovby F, Schwartz M. Carbohydrate-deficient glycoprotein syndrome type 1A: expression and characterisation of wild type and mutant PMM2 in E. coli. Eur J Hum Genet. 1999;7(8):884–8.

    Article  CAS  PubMed  Google Scholar 

  13. Van Schaftingen E, Jaeken J. Phosphomannomutase deficiency is a cause of carbohydrate-deficient glycoprotein syndrome type I. FEBS Lett. 1995;377(3):318–20.

    Article  PubMed  Google Scholar 

  14. Milardi D, Pappalardo M, Grasso DM, la Rosa C. Unveiling the unfolding pathway of FALS associated G37R SOD1 mutant: a computational study. Mol BioSyst. 2010;6(6):1032–9.

    Article  CAS  PubMed  Google Scholar 

  15. Altassan R, Witters P, Saifudeen Z, Quelhas D, Jaeken J, Levtchenko E, et al. Renal involvement in PMM2-CDG, a mini-review. Mol Genet Metab. 2018;123(3):292–6.

    Article  CAS  PubMed  Google Scholar 

  16. Jiao X, Qin C, Li J, Qin Y, Gao X, Zhang B, et al. Cytogenetic analysis of 531 Chinese women with premature ovarian failure. Hum Reprod. 2012;27(7):2201–7.

    Article  CAS  PubMed  Google Scholar 

  17. Hu J, et al. A novel FOXL2 mutation in two infertile patients with blepharophimosis-ptosis-epicanthus inversus syndrome. J Assist Reprod Genet. 2019.

  18. Williams SA, Stanley P. Premature ovarian failure in mice with oocytes lacking core 1-derived O-glycans and complex N-glycans. Endocrinology. 2011;152(3):1057–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Williams SA, and Stanley P. Oocyte-specific deletion of complex and hybrid N-glycans leads to defects in preovulatory follicle and cumulus mass development. Reprod. 2009;137(2):321–31.

    Article  CAS  PubMed  Google Scholar 

  20. Lo BKM, Archibong-Omon A, Ploutarchou P, Day AJ, Milner CM, Williams SA. Oocyte-specific ablation of N- and O-glycans alters cumulus cell signalling and extracellular matrix composition. Reprod Fertil Dev. 2019;31(3):529.

    Article  CAS  Google Scholar 

  21. Hayashi M, McGee E, Min G, Klein C, Rose UM, van Duin M, et al. Recombinant growth differentiation factor-9 (GDF-9) enhances growth and differentiation of cultured early ovarian follicles. Endocrinology. 1999;140(3):1236–44.

    Article  CAS  PubMed  Google Scholar 

  22. Dube JL, Wang P, Elvin J, Lyons KM, Celeste AJ, Matzuk MM. The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes. Mol Endocrinol. 1998;12(12):1809–17.

    Article  CAS  PubMed  Google Scholar 

  23. Chan B, Clasquin M, Smolen GA, Histen G, Powe J, Chen Y, et al. A mouse model of a human congenital disorder of glycosylation caused by loss of PMM2. Hum Mol Genet. 2016;25(11):2182–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Schneider A, et al. Successful prenatal mannose treatment for congenital disorder of glycosylation-Ia in mice. Nat Med. 2011;18(1):71–3.

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank all the participants in the study. We are grateful to Jiangwan Group for its support to “construction project of the center of reproductive health” and Dr. Xinyi He for taking the blood sample from the family. H.W.D. was partially supported by grants from National Institutes of Health (R01AR059781, P20GM109036, R01MH107354, R01MH104680, R01GM109068, R01AR069055, U19AG055373, R01DK115679).

Funding

This study was supported by National Key Research and Development Program of China (2017YFC1001100) and National Natural Science Foundation of China (81471453).

Author information

Authors and Affiliations

  1. Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410013, China

    Tianliu Peng, Chao Lv, Hangjing Tan, Yan Wang, Minghua Zeng, Dajing Yi & Hongmei Xiao

  2. Center for Reproductive Health and Systems Biology and Data information, School of Basic Medical Science, Central South University, Changsha, 410013, Hunan, China

    Tianliu Peng, Chao Lv, Hangjing Tan, Yan Wang, Minghua Zeng, Dajing Yi, Hongwen Deng & Hongmei Xiao

  3. Department of Obstetrics and Gynecology, Reproductive Medicine Center, Second Xiangya Hospital of Central South University, Changsha, 410011, China

    Jie Li & Xiaobo Shi

  4. Life of Sciences, Central South University, Changsha, 410013, China

    Jiafeng Huang & Hailun He

  5. Center for Genomics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA

    Hongwen Deng

Authors
  1. Tianliu Peng
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  2. Chao Lv
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  3. Hangjing Tan
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  4. Jiafeng Huang
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  5. Hailun He
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  6. Yan Wang
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  7. Minghua Zeng
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  8. Dajing Yi
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  9. Jie Li
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  10. Hongwen Deng
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  11. Xiaobo Shi
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  12. Hongmei Xiao
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Corresponding authors

Correspondence to Xiaobo Shi or Hongmei Xiao.

Ethics declarations

Each participating member signed an informed consent form. This study was approved by the Ethics Committee of Central South University.

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The authors declare that they have no conflicts of interest.

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Peng, T., Lv, C., Tan, H. et al. Novel PMM2 missense mutation in a Chinese family with non-syndromic premature ovarian insufficiency. J Assist Reprod Genet 37, 443–450 (2020). https://doi.org/10.1007/s10815-019-01675-8

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  • DOI: https://doi.org/10.1007/s10815-019-01675-8

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