Skip to main content
SpringerLink
Log in

CFTR Gene Variants and Genotypes in Russian Patients with CBAVD Syndrome

  • HUMAN GENETICS
  • Published:
Russian Journal of Genetics Aims and scope Submit manuscript

Abstract

CBAVD syndrome is one of the common genetic causes of male infertility, associated with obstructive azoospermia, commonly resulting from pathogenic CFTR gene variants. We examined 72 Russian infertile men with CBAVD syndrome. Molecular analysis of the CFTR gene was performed to detect 22 common pathogenic variants using AFPL and MLPA. IVS8Tn polymorphism in intron 8 of the CFTR gene was analyzed by “nested” PCR. Pathogenic variants were detected in 47 of 72 (65.3%) patients. The most common CFTR gene variants were F508del, CFTRdele2,3(21kb), and W1282X, which are 54.2, 12.5, and 8.2% of all detected pathogenic variants in examined individuals, respectively. The allele 5T (IVS8-T5) variant was found in 39 (54.2%) patients. Totally, pathogenic variants and/or 5T (IVS8-5T) allele of the CFTR gene were detected in 59 of 72 (81.9%) Russian men with CBAVD syndrome. Two CBAVD-related CFTR gene variants, including the 5T allele, were revealed in 32 (44.4%) patients. The results show a high frequency of pathogenic variants and 5T allele (IVS8-T5) polymorphism of the CFTR gene among Russian men with CBAVD syndrome. Russian patients with CBAVD syndrome and cystic fibrosis share the spectrum of pathogenic gene variants, and the prevalence of the 5Т allele and CFTR genotypes are similar to CBAVD patients from other populations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.

Similar content being viewed by others

REFERENCES

  1. Claustres, M., Molecular pathology of the CFTR locus in male infertility, Reprod. Biomed. Online, 2005, vol. 10, no. 1, pp. 14—41.

    Article  CAS  Google Scholar 

  2. Chen, H., Ruan, Y.C., Xu, W.M., et al., Regulation of male fertility by CFTR and implications in male infertility, Hum. Reprod. Update, 2012, vol. 18, pp. 703—713. https://doi.org/10.1093/humupd/dms027

    Article  CAS  PubMed  Google Scholar 

  3. Schwiebert, E.M., Benos, D.J., Egan, M.E., et al., CFTR is a conductance regulator as well as a chloride channel, Physiol. Rev., 1999, vol. 79, suppl. 1, pp. S145—S166. https://doi.org/10.1152/physrev.1999.79.1.S145

    Article  CAS  PubMed  Google Scholar 

  4. Riordan, J.R., Rommens, J.M., Kerem, B., et al., Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA, Science, 1989, vol. 245, pp. 1066—1073.

    Article  CAS  Google Scholar 

  5. Welsh, M.J. and Smith, A.E., Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis, Cell, 1993, vol. 73, pp. 1252—1254.

    Article  Google Scholar 

  6. Chillon, M., Casals, T., Mercier, B., et al., Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens, N. Eng. J. Med., 1995, vol. 332, pp. 1475—1480. https://doi.org/10.1056/NEJM199506013322204

    Article  CAS  Google Scholar 

  7. Cuppens, H., Lin, W., Jaspers, M., et al., Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes: the polymorphic (TG)m locus explains the partial penetrance of the T5 polymorphism as a disease mutation, J. Clin. Invest., 1998, vol. 101, pp. 487—196. https://doi.org/10.1172/JCI639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Yang, B., Wang, J., Zhang, W., et al., Pathogenic role of ADGRG2 in CBAVD patients replicated in Chinese population, Andrology, 2017, vol. 5, no. 5, pp. 954—957. https://doi.org/10.1111/andr.12407

    Article  CAS  PubMed  Google Scholar 

  9. Patat, O., Pagin, A., Siegfried, A., et al., Truncating mutations in the adhesion G protein-coupled receptor G2 gene ADGRG2 cause an X-Linked congenital bilateral absence of vas deferens, Am. J. Hum. Genet., 2016, vol. 99, no. 2, pp. 437—442. https://doi.org/10.1016/j.ajhg.2016.06.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. WHO Laboratory Manual for the Examination and Processing of Human Semen, Genova: WHO, 2010, 5th ed.

  11. Chernykh, V.B., Stepanova, A.A., Beskorovainaya, T.S., et al., The frequency and spectrum of mutations and the IVS8-T polymorphism of the CFTR gene in Russian infertile men, Russ. J. Genet., 2010, vol. 46, no. 6, pp. 750—757. https://doi.org/10.1134/S1022795410060165

    Article  CAS  Google Scholar 

  12. Dörk, T., Dworniczak, B., Aulehla-Scholz, М., et al., Distinct spectrum of CFTR gene mutations in congenital absence of vas deferens, Hum. Genet., 1997, vol. 100, nos. 3—4, pp. 365—377.

    Article  Google Scholar 

  13. Casals, T., Bassas, L., Egozcue, S., et al., Heterogeneity for mutations in the CFTR gene and clinical correlations in patients with congenital absence of the vas deferens, Hum. Reprod., 2000, vol. 15, no. 7, pp. 1476—1483.

    Article  CAS  Google Scholar 

  14. Claustres, M., Guittard, C., Bozon, D., et al., Spectrum of CFTR mutations in cystic fibrosis and in congenital absence of the vas deferens in France, Hum. Mutat., 2000, vol. 16, pp. 143—156. https://doi.org/10.1002/1098-1004(200008)16:2<143::AID-HUMU7>3.0.CO;2-J

    Article  CAS  PubMed  Google Scholar 

  15. Schwarzer, J.U. and Schwarz, M., Significance of CFTR gene mutations in patients with congenital aplasia of vas deferens with special regard to renal aplasia, Andrologia, 2012, vol. 44, no. 5, pp. 305—307. https://doi.org/10.1111/j.1439-0272.2012.01281.x

    Article  CAS  PubMed  Google Scholar 

  16. Wu, C.C., Hsieh-Li, H.M., Lin, Y.M., et al., Cystic fibrosis transmembrane conductance regulator gene screening and clinical correlation in Taiwanese males with congenital bilateral absence of the vas deferens, Hum. Reprod., 2004, vol. 19, no. 2, pp. 250—253.

    Article  CAS  Google Scholar 

  17. Sharma, N., Acharya, N., Singh, S.K., et al., Heterogeneous spectrum of CFTR gene mutations in Indian patients with congenital absence of vas deferens, Hum. Reprod., 2009, vol. 24, no. 5, pp. 1229—1236. https://doi.org/10.1093/humrep/den500

    Article  CAS  PubMed  Google Scholar 

  18. Anzai, C., Morokawa, N., Okada, H., et al., CFTR gene mutations in Japanese individuals with congenital bilateral absence of the vas deferens, J. Cyst. Fibros., 2003, vol. 2, no. 1, pp. 141—148. https://doi.org/10.1016/S1569-1993(02)00144-3

    Article  CAS  Google Scholar 

  19. Li, H., Wen, Q., Zhao, L., et al., Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) in Chinese patients with congenital bilateral absence of vas deferens, J. Cyst. Fibros., 2012, vol. 11, no. 4, pp. 316—323. https://doi.org/10.1016/j.jcf.2012.01.005

    Article  CAS  PubMed  Google Scholar 

  20. Petrova, N.V., Timkovskaya, E.E., Zinchenko, R.A., and Ginter, E.K., Detection of frequent mutations of gene CFTR in cystic fibrosis patients from Central Russia, Med. Genet., 2006, no. 2, pp. 28—31.

  21. Yu, J., Chen, Z., Ni, Y., and Li, Z., CFTR mutations in men with congenital bilateral absence of the vas deferens (CBAVD): a systemic review and meta-analysis, Hum. Reprod., 2012, vol. 27, no. 1, pp. 25—35. https://doi.org/10.1093/humrep/der377

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

There was no source of funding. This work was carried out as part of the state task of the Ministry of Education and Science of the Russian Federation for Research Centre for Medical Genetics.

Author information

Authors and Affiliations

  1. Pirogov Russian National Research Medical University, 117997, Moscow, Russia

    E. G. Marnat, T. A. Adyan, T. S. Beskorovainaya & V. B. Chernykh

  2. Bochkov Research Centre for Medical Genetics, 115522, Moscow, Russia

    T. A. Adyan, A. A. Stepanova, T. S. Beskorovainaya, A. V. Polyakov & V. B. Chernykh

Authors
  1. E. G. Marnat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. A. Adyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. A. Stepanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. S. Beskorovainaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. V. Polyakov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. B. Chernykh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. B. Chernykh.

Ethics declarations

Conflict of interest. The authors declare that they have no conflict of interest.

Statement of compliance with standards of research involving humans as subjects. All procedures performed in a study involving people comply with the ethical standards of the institutional and/or national committee on research ethics and the Helsinki Declaration of 1964 and its subsequent changes or comparable standards of ethics. All subjects signed an informed consent. The protocol of the study was approved at the ethics committee meeting of the Research Centre for Medical Genetics, Moscow, dated September 4, 2017, protocol no. 5/2.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Marnat, E.G., Adyan, T.A., Stepanova, A.A. et al. CFTR Gene Variants and Genotypes in Russian Patients with CBAVD Syndrome. Russ J Genet 56, 496–501 (2020). https://doi.org/10.1134/S1022795420040055

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1022795420040055

Keywords:

Search

Navigation