Prospects for using exome sequencing to solve problems in human reproduction (Part II)

Glotov O.S., Chernov A.N., Glotov A.S., Baranov V.S.

1) D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology, Saint Petersburg, Russia; 2) Pediatric Research and Clinical Center for Infectious Diseases, Federal Biomedical Agency, Saint Petersburg, Russia
Part 2 of the review considers various purposes of exome (targeted) sequencing to find the causes of reproductive losses, as well as the difficulties of using NGS in reproduction. The authors present their own data and literature ones on the use of NGS to identify lethal fetal phenotypes caused by autosomal recessive monogenic disorders (α-thalassemia; multiple pterygium syndrome, galactosialidosis; mucopolysaccharidosis type VII), autosomal dominant ones (thanatophoric dysplasia; type 2 osteogenesis imperfecta; achondroplasia; tuberous sclerosis 1) and X-linked diseases (incontinentia pigmenti, Goltz syndrome, Rett syndrome, immune dysregulation, polyendocrinopathy, and enteropathy). They thoroughly consider the use of NGS for preconception screening that allows optimization of algorithms to manage a future pregnancy: the choice of diagnostic procedures; recommendations for therapeutic abortion; counseling, pregnancy planning, donation, and prenatal genetic testing. The paper presents the features of and prospects for the introduction of NGS in practical reproductology.
Conclusion: It is necessary to introduce exome sequencing in accordance with the concept of a clinical genetic reproduction passport, especially at the preconception stage, along with the already expanding neonatal screening, which will be able to increase birth rates, to ensure a safe pregnancy, and to enhance the reproductive potential of the Russian population.


reproduction genetics
reproductive losses
preconception screening
clinical genetic passport
monogenic diseases


  1. Khera A.V., Chaffin M., Aragam K.G., Haas M.E., Roselli C., Choi S.H. et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet. 2018; 50: 1219-24.
  2. Pushpakom S., Iorio F., Eyers P.A., Escott K.J., Hopper S., Wells A. et al. Drug repurposing: progress, challenges and recommendations. Nat. Rev. Drug Discov. 2019; 18(1): 41-58.
  3. Capalbo A., Poli M., Riera-Escamilla A., Shukla V., Kudo Høffding M., Krausz C. et al. Preconception genome medicine: current state and future perspectives to improve infertility diagnosis and reproductive and health outcomes based on individual genomic data. Hum. Reprod. Update. 2021; 27(2): 254-79.
  4. Mascarenhas M.N., Flaxman S.R., Boerma T., Vanderpoel S., Stevens G.A. National, regional, and global trends in infertility prevalence . since 1990: a systematic analysis of 277 health surveys. PLoS Med. 2012 ;9: e1001356.
  5. Rajcan-Separovic E. Next generation sequencing in recurrent pregnancy loss-approaches and outcomes. Eur. J. Med. Genet. 2020; 63(2): 103644.
  6. Filges I., Nosova E., Bruder E., Tercanli S., Townsend K., Gibson W.T. et al. Exome sequencing identifies mutations in KIF14 as a novel cause of an autosomal recessive lethal fetal ciliopathy phenotype. Clin. Genet. 2014; 86 (3): 220-8.
  7. Reilly M.L., Stokman M.F., Magry V., Jeanpierre C., Alves M., Paydar M. et al. Loss of function mutations in KIF14 cause severe microcephaly and kidney development defects in humans and zebrafish. Hum. Mol. Genet. 2019; 28(5): 778-95.
  8. Qiao Y., Wen J., Tang F., Martell S., Shomer N., Leung P.C. et al. Whole exome sequencing in recurrent early pregnancy loss. Mol. Hum. Reprod. 2016; 22(5): 364-72.
  9. Rae W., Gao Y., Bunyan D., Holden S., Gilmour K., Patel S. et al. A novel FOXP3 mutation causing fetal akinesia and recurrent male miscarriages. Clin. Immunol. 2015; 161(2): 284-5.
  10. Shamseldin H.E., Kurdi W., Almusafri F., Alnemer M., Alkaff A., Babay Z. et al. Molecular autopsy in maternal-fetal medicine. Genet. Med. 2018; 20(4): 420-7.
  11. Fu M., Mu S., Wen C., Jiang S., Li L., Meng Y. et al. Wholeexome sequencing analysis of products of conception identifies novel mutations associated with missed abortion. Mol. Med. Rep. 2018; 18(2): 2027-32.
  12. Stals K.L., Wakeling M., Baptista J., Caswell R., Parrish A., Rankin J. et al. Diagnosis of lethal or prenatal-onset autosomal recessive disorders by parental exome sequencing. Prenat. Diagn. 2018; 38(1): 33-43.
  13. Quintero-Ronderos P., Mercier E., Fukuda M., Gonzalez R., Suarez C.F., Patarroyo M.A. et al. Novel genes and mutations in patients affected by recurrent pregnancy loss. PLoS One. 2017; 12(10): e0186149.
  14. Chen Y., Bartanus J., Liang D., Zhu H., Breman A.M., Smith J.L. et al. Characterization of chromosomal abnormalities in pregnancy losses reveals critical genes and loci for human early development. Hum. Mutat. 2017; 38(6): 669-77.
  15. Liu H., Mao B., Xu X., Liu L., Ma X., Zhang X. The effectiveness of next-generation sequencing-based preimplantation genetic testing for balanced translocation couples. Cytogenet. Genome Res. 2020; 160(11-12): 625-33.
  16. Chong J.X., Buckingham K.J., Jhangiani S.N., Boehm C., Sobreira N., Smith J.D. et al. The genetic basis of mendelian phenotypes: discoveries, challenges, and opportunities. Am. J. Hum. Genet. 2015; 97: 199-215.
  17. Fridman H., Yntema H. G., Mägi R., Andreson R., Metspalu A., Mezzavila M. et al. The landscape of autosomal-recessive pathogenic variants in European populations reveals phenotype-specific effects. Am. J. Hum. Genet. 2021; 108(4): 608-19.
  18. Hamamy H., Antonarakis S. E., Cavalli-Sforza L.L., Temtamy S., Romeo G., Kate L.P. et al. Consanguineous marriages, pearls and perils: Geneva international consanguinity workshop report. Genet. Med. 2011; 13: 841-7.
  19. Лязина Л.В., Бодюль Н.Н., Вохмянина Н.В., Ефимова А.Г., Серебрякова Е.А., Иващенко Т.Э., Глотов О.С., Глотов А.С., Романова О.В., Куранова М.Л., Василишина А.А., Суспицын Е.Н., Михайлов А.В., Сарана А.М., Щербак С.Г., Баранов В.С. Возможности оказания медицинской помощи в современных условиях на примере семьи с наследственной патологией. Медицинская генетика. 2017; 16(10): 51-4. [Liazina L.V., Bodioul N.N., Vochkmianina N.V., Efimova A.G., Serebryakova E.A., Ivashchenko T.E., Glotov O.S., Glotov A.S., Romanova O.V., Kuranova M.L., Vasilishina A.A., Suspitsin E.N., Mikhailov A.V., Sarana A.M., Shcherbak S.G., Baranov V.S. Modern opportunities of medical care in a family with hereditary disease: a case report. Medical Genetics. 2017;16(10):51-54. (in Russian)].
  20. de Wert G., Dondorp W., Clarke A., Dequeker E.M.C., Cordier C., Deans Z. et al. Opportunistic genomic screening. Recommendations of the European Society of Human Genetics. Eur. J. Hum. Genet. 2021; 29(3): 365-77.
  21. Cousens N.E., Gaff C.L., Metcalfe S.A., Delatycki M.B. Carrier screening for beta-thalassaemia: a review of international practice. Eur. J. Hum. Genet. 2010; 18(10): 1077-83.
  22. Calhaz-Jorge C., De Geyter C., Kupka M.S., de Mouzon J., Erb K., Mocanu E. et al. Assisted reproductive technology in Europe, 2013: results generated from European registers by ESHRE. Hum. Reprod. 2017; 32(10): 1957-73.
  23. Martin J., Asan Yi Y., Alberola T., Rodriguez-Iglesias B., Jimenez-Almazan J., Li Q. et al. Comprehensive carrier genetic test using next-generation deoxyribonucleic acid sequencing in infertile couples wishing to conceive through assisted reproductive technology. Fertil. Steril. 2015; 104(5): 1286-93.
  24. Henneman L., Borry P., Chokoshvili D., Cornel M.C., van El C.G., Forzano F. et al Responsible implementation of expanded carrier screening. Eur. J. Hum. Genet. 2016; 24: e1-e12.

Received 19.09.2022

Accepted 02.11.2022

About the Authors

Oleg S. Glotov, PhD, Senior Researcher at the Department of Genomic Medicine, D.O. Ott’s Research Institute Institute of Obstetrics, Gynecology, and Reproductology, 199034, Russia, Saint-Petersburg, Mendeleevskaya line, 3; Head of the Department of Experimental Medical Virology, Molecular Genetics and Biobanking, Pediatric Research and Clinical Center for Infectious Diseases, 197022, Russia, Saint-Petersburg, Professor Popov str., 9,,
Alexander N. Chernov, PhD, Researcher at the Department of Genomic Medicine, D.O. Ott’s Research Institute Institute of Obstetrics, Gynecology, and Reproductology,,, 199034, Russia, Saint-Petersburg, Mendeleevskaya line, 3.
Andrey S. Glotov, Dr. Bio. Sci, Head of the Department of Genomic Medicine, D.O. Ott’s Research Institute of Obstetrics, Gynecology, and Reproductology,,, 199034, Russia, Saint-Petersburg, Mendeleevskaya line, 3.
Vladislav S. Baranov , Dr. Med. Sci., Professor, Corresponding Member of the Russian Academy of Sciences, geneticist of the highest category, Chief Researcher of the Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, +7(921)337-77-96,,
199034, Russia, St. Petersburg, Mendeleevskaya line, 3.
Corresponding author: Oleg S. Glotov,

Authors’ contributions: Glotov O.S., Glotov A.S. – writing the text; Chernov A.N., Baranov V.S. – editing.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The investigation has been supported by the Ministry of Science and Higher Education of the Russian Federation (“Multicenter Research Collection of Bioresources “Human Reproductive Health”” Project; Contract No. 075-15-2021-1058 dated September 28, 2021).
For citation: Glotov O.S., Chernov A.N., Glotov A.S., Baranov V.S. Prospects for using exome sequencing to solve problems in human reproduction (Part II).
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2022; 12: 40-45 (in Russian).

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