Russian Journal of Genetics

, Volume 46, Issue 6, pp 750–757

The frequency and spectrum of mutations and the IVS8-T polymorphism of the CFTR gene in Russian infertile men

  • V. B. Chernykh
  • A. A. Stepanova
  • T. S. Beskorovainaya
  • T. M. Sorokina
  • L. V. Shileiko
  • L. F. Kurilo
  • A. V. Polyakov
Human Genetics


The frequency and spectrum of mutations and the IVS8-T polymorphism of the CFTR gene have been studied in a cohort of 963 in Russian infertile men. Mutations have been found in 48 out of 1926 analyzed chromosomes (2.5%) in the heterozygous state (n = 46) and in the compound heterozygote L138ins/N1303K (n = 1). A CFTR gene mutation was combined with the 5T allele (mutCFTR/5T) in 11 patients. The following mutations have been found: F508del (n = 18), CFTRdele2,3(21kb) (n = 9), W1282X (n = 7), 2143delT (n = 4), 3849 +10kbC>T (n = 2), L138ins (n = 2), 1677delTA (n = 1), 2184insA (n = 1), 3821delT (n = 1), G542X (n = 1), N1303K (n = 1), and R334W (n = 1). The F508del mutation is the most frequent; it has been detected in 37.5% of the affected chromosomes. The total proportion of four mutations (F508del, CFTRdele2,3(21kb), W1282X, and 2143delT) is about 79% of all mutations found. The 5T allele has been found in 10.9% infertile men and 4.8% of control men. Significant differences in the frequency of the IVS8-5T variant of the CFTR gene have been found between these groups (p = 0.005), as well as between infertile patients without mutations and control men (p = 0.019). In total, the mutations and /or 5T allele have been found in 14.6% of the patients examined. These data indicate increased frequencies of the mutations of the CFTR gene and its allele variant IVS8-5T in Russian infertile men.


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  1. 1.
    Kurilo, L.F., Shileiko, L.V., Sorokina, T.M., et al., The Structure of Hereditary Disturbances in Reproductive System, Vestn. Ross. Akad. Med. Nauk, 2000, no. 5, pp. 32–36.Google Scholar
  2. 2.
    Chernykh, V.B., Genetic Factors of Musculine Sterility, in Molekulyarnye metody diagnostiki monogennykh zabolevanii: vozmozhnosti i perspektivy (Molecular Methods of Diagnostics of Monogenic Deseases), Proc. All-Union Theor. Pract. Conf., Med. Genet., 2006, suppl. 2, pp. 8–14.Google Scholar
  3. 3.
    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.CrossRefPubMedGoogle Scholar
  4. 4.
    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.PubMedGoogle Scholar
  5. 5.
    Ivashchenko, T.E. and Baranov, V.S., Biokhimicheskie i molekulyarno-geneticheskie osnovy patogeneza mukovistsidoza (Biochemical and Molecular-Genetic Aspects of Pathogenesis of Cystic Fibrosis), St. Petersburg: Intermedika, 2002.Google Scholar
  6. 6.
    Welsh, M.J. and Smith, A.E., Molecular Mechanisms of CFTR Chloride Channel Dysfunction in Cystic Fibrosis, Cell, 1993, vol. 73, pp. 1252–1254.CrossRefGoogle Scholar
  7. 7.
    Kerem, B. and Kerem, E., The Molecular Basis for Disease Variability in Cystic Fibrosis, Eur. J. Hum. Genet., 1996, vol. 4, pp. 65–73.PubMedGoogle Scholar
  8. 8.
    Tsui, L.C., The Spectrum of Cystic Fibrosis Mutation, Trends Genet., 1992, vol. 8, pp. 392–398.PubMedGoogle Scholar
  9. 9.
    Kiesewetter, S., Macek, M., Davis, C., et al., A Mutation in CFTR Produces Different Phenotypes Depending on Chromosomal Background, Nat. Genet., 1993, vol. 5, pp. 274–278.CrossRefPubMedGoogle Scholar
  10. 10.
    Kapranov, N.I., Kashirskaya, N.Yu., and Petrova, H.V., Cystic Fibrosis: Last Achievements and Modern Problems, Med. Genet., 2004, no. 9, pp. 398–412.Google Scholar
  11. 11.
    Potapova, O.Yu., Molecular Genetic Analysis of Cystic Fibrosis in Russia, Extended Abstract of Cand. Sci. Dissertation, NIIEM Russian Acad. Med. Sci., St. Petersburg, 1994, p. 21.Google Scholar
  12. 12.
    Ivashchenko, T.E., Cystic Fibrosis: Molecular Genetic Analysis of the CFTR Gene, Elaboration of New Approaches to Diagnostics and Therapy, Extended Abstract of Doctoral Dissertation, Moscow, 2000, p. 46.Google Scholar
  13. 13.
    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.Google Scholar
  14. 14.
    Petrova, N.V., Molecular Genetic Specificity of Cystic Fibrosis in Russian Populations, Doctoral (Biol.) Dissertation, Moscow: GU MGNTs Russian Acad. Med. Sci., 2009, p. 40.Google Scholar
  15. 15.
    Kaplan, E., Shwachman, H., Perlmutter, A.D., et al., Reproductive Failure in Males with Cystic Fibrosis, New Eng. J. Med., 1968, vol. 279, pp. 65–69.PubMedGoogle Scholar
  16. 16.
    Jequier, A.M., Amell, I.D., and Bultimore, N.J., Congenital Absence of the vas deferentia Presenting with Fertility, J. Androl., 1985, vol. 6, pp. 15–19.PubMedGoogle Scholar
  17. 17.
    Anguiano, A., Oates, R.D., Amos, J.A., et al., Congenital Bilateral Absence of the vas deferens: A Primarily Genital Form of Cystic Fibrosis, JAMA, 1992, vol. 267, pp. 1794–1797.CrossRefPubMedGoogle Scholar
  18. 18.
    Mercier, B., Verlingue, C., Lissens, W., et al., Is Congenital Bilateral Absence of vas deferens a Primary Form of Cystic Fibrosis? Analyses of the CFTR Gene in 67 Patients, Am. J. Hum. Genet., 1995, vol. 56, pp. 272–277.PubMedGoogle Scholar
  19. 19.
    Durieu, I., Bey-Omar, F., Rollet, J., et al., Male Infertility Caused by Bilateral Agenesis of the vas deferens: A New Clinical Form of Cystic Fibrosis?, Rev. Med. Interne, 1997, vol. 18, no. 2, pp. 114–118.CrossRefPubMedGoogle Scholar
  20. 20.
    Blau, H., Freud, E., Mussaffi, H., et al., Urogenital Abnormalities in Male Children with Cystic Fibrosis, Arch. Dis. Child., 2002, vol. 87, pp. 135–138.CrossRefPubMedGoogle Scholar
  21. 21.
    Chillon, M., Casals, T., Mercier, B., et al., Mutations in the Cystic Fibrosis Gene in Patients with Congenital Absence of the vas deferens, New Eng. J. Med., 1995, vol. 332, pp. 1475–1480.CrossRefPubMedGoogle Scholar
  22. 22.
    Braekeleer, M. and Ferec, C., Mutations in the Cystic Fibrosis Gene in Men with Congenital Bilateral Absence of the vas deferens, Mol. Hum. Reprod., 1996, vol. 2, pp. 669–677.CrossRefPubMedGoogle Scholar
  23. 23.
    Dumur, V., Gervais, R., Rigot, J.-M., et al., Congenital Bilateral Absence of the vas deferens (CBAVD) and Cystic Fibrosis Transmembrane Regulator (CFTR): Correlation between Genotype and Phenotype, Hum. Genet., 1996, vol. 97, pp. 7–10.CrossRefPubMedGoogle Scholar
  24. 24.
    Dörk, T., Dworniczak, B., Aulehla-Scholz, C., et al., Distinct Spectrum of CFTR Gene Mutations in Congenital Absence of vas deferens, Hum. Genet., 1997, vol. 100, pp. 365–377.CrossRefPubMedGoogle Scholar
  25. 25.
    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.CrossRefPubMedGoogle Scholar
  26. 26.
    Claustres, M., Molecular Pathology of the CFTR Locus in Male Infertility, Reprod. Biomed. Online, 2005, vol. 10, pp. 14–41.CrossRefPubMedGoogle Scholar
  27. 27.
    Chu, C.S., Trapnell, B.C., Curristin, S.M., et al., Genetic Basis of Variable Exon Skipping in Cystic Fibrosis Transmembrane Conductance Regulator mRNA, Nat. Genet., 1993, vol. 3, pp. 151–156.CrossRefPubMedGoogle Scholar
  28. 28.
    Teng, H., Jorissen, M., Van Poppel, H., et al., Increased Proportion of Exon 9 Alternatively Spliced CFTR Transcripts in vas deferens Compared with Nasal Epithelial Cells, Hum. Mol. Genet., 1997, vol. 6, pp. 85–90.CrossRefPubMedGoogle Scholar
  29. 29.
    Disset, A., Michot, C., Harris, A., et al., A T3 Allele in the CFTR Gene Exacerbates Exon 9 Skipping in vas deferens and Epididymal Cell Lines and Is Associated with Congenital Bilateral Absence of vas deferens (CBAVD), Hum. Mutat., 2005, vol. 25, pp. 72–81.CrossRefPubMedGoogle Scholar
  30. 30.
    Huang, Q., Ding, W., and Wei, M.X., Comparative Analysis of Common CFTR Polymorphisms Poly-T, TG-Repeats and M470V in a Healthy Chinese Population, World J. Gastroenterol., 2008, vol. 14, pp. 1925–1930.CrossRefPubMedGoogle Scholar
  31. 31.
    Radpour, R., Taherzadeh-Fard, E., Gourabi, H., et al., Novel Cause of Hereditary Obstructive Azoospermia: A T2 Allele in the CFTR Gene, Reprod. Biomed. Online, 2009, vol. 18, pp. 327–332.CrossRefPubMedGoogle Scholar
  32. 32.
    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. 487–496.CrossRefPubMedGoogle Scholar
  33. 33.
    Morea, A., Cameran, M., Rebuffi, A.G., et al., Gender-Sensitive Association of CFTR Gene Mutations and 5T Allele Emerging from a Large Survey on Infertility, Mol. Hum. Reprod., 2005, vol. 11, pp. 607–614.CrossRefPubMedGoogle Scholar
  34. 34.
    Tamburino, L., Guglielmino, A., Venti, E., et al., Molecular Analysis of Mutations and Polymorphisms in the CFTR Gene in Male Infertility, Reprod. Biomed. Online, 2008, vol. 17, pp. 27–35.CrossRefPubMedGoogle Scholar
  35. 35.
    Glantz, S.A., Primer of Biostatistics, New York: McGraw-Hill, 1997, 4th edition.Google Scholar
  36. 36.
    Dörk, T., Masek, M., Jr., Mekus, F., et al., Characterization of a Novel 21-kb Deletion, CFTRdele2,3(21 kb), in the CFTR Gene: A Cystic Fibrosis Mutation of Slavic Origin Common in Central and East Europe, Hum. Genet., 2000, vol. 106, pp. 259–268.CrossRefPubMedGoogle Scholar
  37. 37.
    Dörk, T., Mekus, F., Schmidt, K., et al., Detection of more than 50 Different CFTR Mutations in a Large Group of German Cystic Fibrosis Patients, Hum. Genet., 1994, vol. 94, pp. 533–542.CrossRefPubMedGoogle Scholar
  38. 38.
    Cuppens, H., Teng, H., Raeymaekers, P., et al., CFTR Haplotype Backgrounds on Normal and Mutant CFTR Genes, Hum. Mol. Genet., 1994, vol. 3, pp. 607–614.CrossRefPubMedGoogle Scholar
  39. 39.
    Dörk, T., Fislage, R., Neumann, T., et al., Exon 9 of the CFTR Gene: Splice Site Haplotypes and Cystic Fibrosis Mutations, Hum. Genet., 1994, vol. 93, pp. 67–73.CrossRefPubMedGoogle Scholar
  40. 40.
    Xu, W.M., Shi, Q.X., Chen, W.Y., et al., Cystic Fibrosis Transmembrane Conductance Regulator Is Vital to Sperm Fertilizing Capacity and Male Fertility, Proc. Natl. Acad. Sci. USA, 2007, vol. 104, pp. 9816–9821.CrossRefPubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2010

Authors and Affiliations

  • V. B. Chernykh
    • 1
  • A. A. Stepanova
    • 1
  • T. S. Beskorovainaya
    • 1
  • T. M. Sorokina
    • 1
  • L. V. Shileiko
    • 1
  • L. F. Kurilo
    • 1
  • A. V. Polyakov
    • 1
  1. 1.Research Center for Medical GeneticsRussian Academy of Medical SciencesMoscowRussia

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