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Copy Number Variation Analysis in Turkish Patients with Congenital Bilateral Absence of Vas Deferens

Yıl 2021, Cilt: 5 Sayı: 2, 181 - 189, 30.08.2021
https://doi.org/10.30565/medalanya.966940

Öz

Aim: Congenital Bilateral Absence of the Vas Deferens (CBAVD) is a developmental abnormality that causes infertility in males. According to the literature, up to 88% of CBAVD cases have at least one pathogenic Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) mutation. However, based on our previous data, this rate was 15.90% in Turkish patients with CBAVD. We aimed to identify genomic copy number variations (CNV) and candidate genomic regions which could related to the CBAVD in Turkish population.

Methods: CNV analysis was performed in 19 Turkish CBAVD patients normal karyotypes and a wild type CFTR genotype. We suggested that the DAD1 gene may be a candidate gene related to CBAVD by reviewing online databases and analyzing CNV findings. Sanger sequencing of the DAD1 gene exons was performed in 22 patients.

Results: We identified 11 CNVs that most likely related with the disease in nine of 19 (47.3%) patients. As the most common CNV, 14q11.2 deletions were detected in there (15.79%) of the patients. There was only DAD1 gene in the sharing genomic region of two of the 14q11.2 deletions. No sequence variation was detected in the DAD1 gene of the patients.

Conclusion: The 14q11.2 chromosomal region and the DAD1 gene may be associated with CBAVD. Further studies are needed to indentify the contribution of CNVs and DAD1 gene to CBAVD etiology.

Destekleyen Kurum

TÜBİTAK

Proje Numarası

SBAG-115S171

Teşekkür

We are thankful to the patients who participated in the study. We also thank Dr. Lynn P. Chorich for checking the spelling.

Kaynakça

  • 1. Kumar N, Singh AK. Trends of male factor infertility, an important cause of infertility: A review of literature. J Hum Reprod Sci. 2015;8(4):191-6. doi: 10.4103/0974-1208.170370.
  • 2. Lidegaard O, Mikkelsen AL, Meldgaard M, Brondum-Nielsen K, Lindenberg S. Severe male infertility. Impact of genetic factors on diagnosis and counselling. Acta Obstet Gynecol Scand. 1998;77(8):799-803. PMID: 9776591.
  • 3. Lee CH, Wu CC, Wu YN, Chiang HS. Gene copy number variations in Asian patients with congenital bilateral absence of the vas deferens. Human reproduction. 2009;24(3):748-55. doi: 10.1093/humrep/den413.
  • 4. Yu J, Chen Z, Ni Y, Li Z. CFTR mutations in men with congenital bilateral absence of the vas deferens (CBAVD): a systemic review and meta-analysis. Human reproduction. 2012;27(1):25-35. doi: 10.1093/humrep/der377.
  • 5. Ocak Z, Uyetuork U, Dincer MM. Clinical and prognostic importance of chromosomal abnormalities, Y chromosome microdeletions, and CFTR gene mutations in individuals with azoospermia or severe oligospermia. Turk J Med Sci. 2014;44(2):347-51. PMID: 25536748.
  • 6. Dayangac D, Erdem H, Yilmaz E, Sahin A, Sohn C, Ozguc M, et al. Mutations of the CFTR gene in Turkish patients with congenital bilateral absence of the vas deferens. Human reproduction. 2004;19(5):1094-100. doi: 10.1093/humrep/deh223.
  • 7. Akin Y, Demir D, Gorgisen G, Luleci G, Alper OM, Watanabe CS, et al. Novel and rare CFTR gene mutations in Turkish patients with congenital aplasia of vas deferens. Andrologia. 2014;46(2):198-9. doi: 10.1111/and.12053.
  • 8. Patat O, Pagin A, Siegfried A, Mitchell V, Chassaing N, Faguer S, 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;99(2):437-42. doi: 10.1016/j.ajhg.2016.06.012.
  • 9. Yang B, Wang J, Zhang W, Pan H, Li T, Liu B, et al. Pathogenic role of ADGRG2 in CBAVD patients replicated in Chinese population. Andrology. 2017;5(5):954-7. doi: 10.1111/andr.12407.
  • 10. Shen Y, Yue HX, Li FP, Hu FY, Li XL, Wan Q, et al. SCNN1B and CA12 play vital roles in occurrence of congenital bilateral absence of vas deferens (CBAVD). Asian J Androl. 2019. doi: 10.4103/aja.aja_112_18.
  • 11. Wu YN, Chen KC, Wu CC, Lin YH, Chiang HS. SLC9A3 Affects Vas Deferens Development and Associates with Taiwanese Congenital Bilateral Absence of the Vas Deferens. BioMed research international. 2019;2019:3562719. doi: 10.1155/2019/3562719.
  • 12. Hodoglugil U, Mahley RW. Turkish population structure and genetic ancestry reveal relatedness among Eurasian populations. Ann Hum Genet. 2012;76(2):128-41. doi: 10.1111/j.1469-1809.2011.00701.x.
  • 13. Zhang F, Gu W, Hurles ME, Lupski JR. Copy number variation in human health, disease, and evolution. Annu Rev Genomics Hum Genet. 2009;10:451-81. doi: 10.1146/annurev.genom.9.081307.164217.
  • 14. Eggers S, DeBoer KD, van den Bergen J, Gordon L, White SJ, Jamsai D, et al. Copy number variation associated with meiotic arrest in idiopathic male infertility. Fertility and sterility. 2015;103(1):214-9. doi: 10.1016/j.fertnstert.2014.09.030.
  • 15. Dong Y, Pan Y, Wang R, Zhang Z, Xi Q, Liu RZ. Copy number variations in spermatogenic failure patients with chromosomal abnormalities and unexplained azoospermia. Genet Mol Res. 2015;14(4):16041-9. doi: 10.4238/2015.December.7.17.
  • 16. Makishima T, Nakashima T, Nagata-Kuno K, Fukushima K, Iida H, Sakaguchi M, et al. The highly conserved DAD1 protein involved in apoptosis is required for N-linked glycosylation. Genes Cells. 1997;2(2):129-41. doi: 10.1046/j.1365-2443.1997.1070303.x.
  • 17. Lahiri DK, Nurnberger JI, Jr. A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res. 1991;19(19):5444. doi: 10.1093/nar/19.19.5444.
  • 18. Riggs ER, Andersen EF, Cherry AM, Kantarci S, Kearney H, Patel A, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020;22(2):245-57. doi: 10.1038/s41436-019-0686-8.
  • 19. Roboti P, High S. The oligosaccharyltransferase subunits OST48, DAD1 and KCP2 function as ubiquitous and selective modulators of mammalian N-glycosylation. J Cell Sci. 2012;125(Pt 14):3474-84. doi: 10.1242/jcs.103952.
  • 20. Brewster JL, Martin SL, Toms J, Goss D, Wang K, Zachrone K, et al. Deletion of Dad1 in mice induces an apoptosis-associated embryonic death. Genesis. 2000;26(4):271-8.
  • 21. Glozman R, Okiyoneda T, Mulvihill CM, Rini JM, Barriere H, Lukacs GL. N-glycans are direct determinants of CFTR folding and stability in secretory and endocytic membrane traffic. J Cell Biol. 2009;184(6):847-62. doi: 10.1083/jcb.200808124.
  • 22. Shaikh TH. Copy Number Variation Disorders. Curr Genet Med Rep. 2017;5(4):183-90. doi: 10.1007/s40142-017-0129-2.
  • 23. Demir Eksi D, Shen Y, Erman M, Chorich LP, Sullivan ME, Bilekdemir M, et al. Copy number variation and regions of homozygosity analysis in patients with MULLERIAN aplasia. Mol Cytogenet. 2018;11:13. doi: 10.1186/s13039-018-0359-3.
  • 24. Williams LS, Demir Eksi D, Shen Y, Lossie AC, Chorich LP, Sullivan ME, et al. Genetic analysis of Mayer-Rokitansky-Kuster-Hauser syndrome in a large cohort of families. Fertility and sterility. 2017;108(1):145-51 e2. doi: 10.1016/j.fertnstert.2017.05.017.
  • 25. Bieth E, Hamdi SM, Mieusset R. Genetics of the congenital absence of the vas deferens. Hum Genet. 2021;140(1):59-76. doi: 10.1007/s00439-020-02122-w.
  • 26. Lin CH, Huang TY. Congenital bilateral absence of the vas deferens (CBAVD) with bilaterally present seminal vesicles. Urol Case Rep. 2020;31:101131. doi: 10.1016/j.eucr.2020.101131.
  • 27. van der Ven K, Messer L, van der Ven H, Jeyendran RS, Ober C. Cystic fibrosis mutation screening in healthy men with reduced sperm quality. Human reproduction. 1996;11(3):513-7. doi: 10.1093/humrep/11.3.513.
  • 28. Wedenoja S, Khamaysi A, Shimshilashvili L, Anbtawe-Jomaa S, Elomaa O, Toppari J, et al. A missense mutation in SLC26A3 is associated with human male subfertility and impaired activation of CFTR. Scientific reports. 2017;7(1):14208. doi: 10.1038/s41598-017-14606-3.
  • 29. Schwarzer JU, Schwarz M. Significance of CFTR gene mutations in patients with congenital aplasia of vas deferens with special regard to renal aplasia. Andrologia. 2012;44(5):305-7. doi: 10.1111/j.1439-0272.2012.01281.x.
  • 30. Gajbhiye R, Kadam K, Khole A, Gaikwad A, Kadam S, Shah R, et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene abnormalities in Indian males with congenital bilateral absence of vas deferens & renal anomalies. Indian J Med Res. 2016;143(5):616-23. doi: 10.4103/0971-5916.187110.
  • 31. Tuttelmann F, Simoni M, Kliesch S, Ledig S, Dworniczak B, Wieacker P, et al. Copy number variants in patients with severe oligozoospermia and Sertoli-cell-only syndrome. PloS one. 2011;6(4):e19426. doi: 10.1371/journal.pone.0019426.
  • 32. Halder A, Kumar P, Jain M, Iyer VK. Copy number variations in testicular maturation arrest. Andrology. 2017;5(3):460-72. doi: 10.1111/andr.12330.
  • 33. Yasin H, Gibson WT, Langlois S, Stowe RM, Tsang ES, Lee L, et al. A distinct neurodevelopmental syndrome with intellectual disability, autism spectrum disorder, characteristic facies, and macrocephaly is caused by defects in CHD8. J Hum Genet. 2019;64(4):271-80. doi: 10.1038/s10038-019-0561-0.
  • 34. Kamnasaran D, Cox DW. Current status of human chromosome 14. Journal of medical genetics. 2002;39(2):81-90. doi: 10.1136/jmg.39.2.81.
  • 35. Rockett JC, Mapp FL, Garges JB, Luft JC, Mori C, Dix DJ. Effects of hyperthermia on spermatogenesis, apoptosis, gene expression, and fertility in adult male mice. Biol Reprod. 2001;65(1):229-39. doi: 10.1095/biolreprod65.1.229.
  • 36. Bansal SK, Gupta N, Sankhwar SN, Rajender S. Differential Genes Expression between Fertile and Infertile Spermatozoa Revealed by Transcriptome Analysis. PloS one. 2015;10(5):e0127007. doi: 10.1371/journal.pone.0127007.
  • 37. Li CY, Jiang LY, Chen WY, Li K, Sheng HQ, Ni Y, et al. CFTR is essential for sperm fertilizing capacity and is correlated with sperm quality in humans. Human reproduction. 2010;25(2):317-27. doi: 10.1093/humrep/dep406.
  • 38. Flannigan R, Schlegel PN. Genetic diagnostics of male infertility in clinical practice. Best Pract Res Clin Obstet Gynaecol. 2017;44:26-37. doi: 10.1016/j.bpobgyn.2017.05.002.

Konjenital Bilateral Vas Deferens Yokluğu Olan Türk Hastalarda Genomik Kopya Sayısı Varyasyonları Analizi

Yıl 2021, Cilt: 5 Sayı: 2, 181 - 189, 30.08.2021
https://doi.org/10.30565/medalanya.966940

Öz

Amaç: Konjenital Bilateral Vas Deferens Yokluğu (CBAVD), erkeklerde infertiliteye yol açan gelişimsel bir anomalidir. Literatüre göre CBAVD’li olguların %88’e kadarı en az bir Kistik Fibrozis Transmembran Regülatör geni (CFTR) mutasyonuna sahiptir. Ancak, daha önceki verilerimize göre CBAVD’li Türk hastalarda bu oran %15.90’dır. Çalışmamız kapsamında Türk popülasyonundaki CBAVD ile ilişkili olabilecek genomik kopya sayısı varyasyonları (CNV) ve aday genomik bölgelerin tanımlanması amaçlanmıştır.

Yöntemler: Normal karyotipe ve yabanıl tip CFTR genotipine sahip 19 Türk CBAVD’li hastanın CNV analizi gerçekleştirildi. CNV bulgularımızın analizi ve veritabanlarının taranması ile DAD1 geni CBAVD ile ilişkili olabilecek potansiyel aday gen olarak tanımlandı. 22 CBAVD’li hastada da DAD1 geni ekzonlarının dizi analizi Sanger dizileme metoduyla yapıldı.

Bulgular: 19 hastanın dokuzunda (%47.3) hastalıkla ilişkili olabilecek 11 adet CNV saptandı. En sık saptanan CNV olarak 14q11.2 delesyonu, hastaların üçünde (%15.79) belirlendi. 14q11.2 delesyonlarından ikisinin ortak varyant bölgesinde yalnızca DAD1 geni lokalize idi. Dizi analizi ile, hastaların DAD1 geninde herhangi bir dizi varyasyonu saptanmadı.

Sonuç: 14q11.2 kromozomal bölgesi ve DAD1 geni CBAVD ile ilişkili olabilir. CNVlerin ve DAD1 geninin CBAVD etiyolojisine katkısını tanımlamak için ileri çalışmalar gerekmektedir.

Proje Numarası

SBAG-115S171

Kaynakça

  • 1. Kumar N, Singh AK. Trends of male factor infertility, an important cause of infertility: A review of literature. J Hum Reprod Sci. 2015;8(4):191-6. doi: 10.4103/0974-1208.170370.
  • 2. Lidegaard O, Mikkelsen AL, Meldgaard M, Brondum-Nielsen K, Lindenberg S. Severe male infertility. Impact of genetic factors on diagnosis and counselling. Acta Obstet Gynecol Scand. 1998;77(8):799-803. PMID: 9776591.
  • 3. Lee CH, Wu CC, Wu YN, Chiang HS. Gene copy number variations in Asian patients with congenital bilateral absence of the vas deferens. Human reproduction. 2009;24(3):748-55. doi: 10.1093/humrep/den413.
  • 4. Yu J, Chen Z, Ni Y, Li Z. CFTR mutations in men with congenital bilateral absence of the vas deferens (CBAVD): a systemic review and meta-analysis. Human reproduction. 2012;27(1):25-35. doi: 10.1093/humrep/der377.
  • 5. Ocak Z, Uyetuork U, Dincer MM. Clinical and prognostic importance of chromosomal abnormalities, Y chromosome microdeletions, and CFTR gene mutations in individuals with azoospermia or severe oligospermia. Turk J Med Sci. 2014;44(2):347-51. PMID: 25536748.
  • 6. Dayangac D, Erdem H, Yilmaz E, Sahin A, Sohn C, Ozguc M, et al. Mutations of the CFTR gene in Turkish patients with congenital bilateral absence of the vas deferens. Human reproduction. 2004;19(5):1094-100. doi: 10.1093/humrep/deh223.
  • 7. Akin Y, Demir D, Gorgisen G, Luleci G, Alper OM, Watanabe CS, et al. Novel and rare CFTR gene mutations in Turkish patients with congenital aplasia of vas deferens. Andrologia. 2014;46(2):198-9. doi: 10.1111/and.12053.
  • 8. Patat O, Pagin A, Siegfried A, Mitchell V, Chassaing N, Faguer S, 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;99(2):437-42. doi: 10.1016/j.ajhg.2016.06.012.
  • 9. Yang B, Wang J, Zhang W, Pan H, Li T, Liu B, et al. Pathogenic role of ADGRG2 in CBAVD patients replicated in Chinese population. Andrology. 2017;5(5):954-7. doi: 10.1111/andr.12407.
  • 10. Shen Y, Yue HX, Li FP, Hu FY, Li XL, Wan Q, et al. SCNN1B and CA12 play vital roles in occurrence of congenital bilateral absence of vas deferens (CBAVD). Asian J Androl. 2019. doi: 10.4103/aja.aja_112_18.
  • 11. Wu YN, Chen KC, Wu CC, Lin YH, Chiang HS. SLC9A3 Affects Vas Deferens Development and Associates with Taiwanese Congenital Bilateral Absence of the Vas Deferens. BioMed research international. 2019;2019:3562719. doi: 10.1155/2019/3562719.
  • 12. Hodoglugil U, Mahley RW. Turkish population structure and genetic ancestry reveal relatedness among Eurasian populations. Ann Hum Genet. 2012;76(2):128-41. doi: 10.1111/j.1469-1809.2011.00701.x.
  • 13. Zhang F, Gu W, Hurles ME, Lupski JR. Copy number variation in human health, disease, and evolution. Annu Rev Genomics Hum Genet. 2009;10:451-81. doi: 10.1146/annurev.genom.9.081307.164217.
  • 14. Eggers S, DeBoer KD, van den Bergen J, Gordon L, White SJ, Jamsai D, et al. Copy number variation associated with meiotic arrest in idiopathic male infertility. Fertility and sterility. 2015;103(1):214-9. doi: 10.1016/j.fertnstert.2014.09.030.
  • 15. Dong Y, Pan Y, Wang R, Zhang Z, Xi Q, Liu RZ. Copy number variations in spermatogenic failure patients with chromosomal abnormalities and unexplained azoospermia. Genet Mol Res. 2015;14(4):16041-9. doi: 10.4238/2015.December.7.17.
  • 16. Makishima T, Nakashima T, Nagata-Kuno K, Fukushima K, Iida H, Sakaguchi M, et al. The highly conserved DAD1 protein involved in apoptosis is required for N-linked glycosylation. Genes Cells. 1997;2(2):129-41. doi: 10.1046/j.1365-2443.1997.1070303.x.
  • 17. Lahiri DK, Nurnberger JI, Jr. A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res. 1991;19(19):5444. doi: 10.1093/nar/19.19.5444.
  • 18. Riggs ER, Andersen EF, Cherry AM, Kantarci S, Kearney H, Patel A, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020;22(2):245-57. doi: 10.1038/s41436-019-0686-8.
  • 19. Roboti P, High S. The oligosaccharyltransferase subunits OST48, DAD1 and KCP2 function as ubiquitous and selective modulators of mammalian N-glycosylation. J Cell Sci. 2012;125(Pt 14):3474-84. doi: 10.1242/jcs.103952.
  • 20. Brewster JL, Martin SL, Toms J, Goss D, Wang K, Zachrone K, et al. Deletion of Dad1 in mice induces an apoptosis-associated embryonic death. Genesis. 2000;26(4):271-8.
  • 21. Glozman R, Okiyoneda T, Mulvihill CM, Rini JM, Barriere H, Lukacs GL. N-glycans are direct determinants of CFTR folding and stability in secretory and endocytic membrane traffic. J Cell Biol. 2009;184(6):847-62. doi: 10.1083/jcb.200808124.
  • 22. Shaikh TH. Copy Number Variation Disorders. Curr Genet Med Rep. 2017;5(4):183-90. doi: 10.1007/s40142-017-0129-2.
  • 23. Demir Eksi D, Shen Y, Erman M, Chorich LP, Sullivan ME, Bilekdemir M, et al. Copy number variation and regions of homozygosity analysis in patients with MULLERIAN aplasia. Mol Cytogenet. 2018;11:13. doi: 10.1186/s13039-018-0359-3.
  • 24. Williams LS, Demir Eksi D, Shen Y, Lossie AC, Chorich LP, Sullivan ME, et al. Genetic analysis of Mayer-Rokitansky-Kuster-Hauser syndrome in a large cohort of families. Fertility and sterility. 2017;108(1):145-51 e2. doi: 10.1016/j.fertnstert.2017.05.017.
  • 25. Bieth E, Hamdi SM, Mieusset R. Genetics of the congenital absence of the vas deferens. Hum Genet. 2021;140(1):59-76. doi: 10.1007/s00439-020-02122-w.
  • 26. Lin CH, Huang TY. Congenital bilateral absence of the vas deferens (CBAVD) with bilaterally present seminal vesicles. Urol Case Rep. 2020;31:101131. doi: 10.1016/j.eucr.2020.101131.
  • 27. van der Ven K, Messer L, van der Ven H, Jeyendran RS, Ober C. Cystic fibrosis mutation screening in healthy men with reduced sperm quality. Human reproduction. 1996;11(3):513-7. doi: 10.1093/humrep/11.3.513.
  • 28. Wedenoja S, Khamaysi A, Shimshilashvili L, Anbtawe-Jomaa S, Elomaa O, Toppari J, et al. A missense mutation in SLC26A3 is associated with human male subfertility and impaired activation of CFTR. Scientific reports. 2017;7(1):14208. doi: 10.1038/s41598-017-14606-3.
  • 29. Schwarzer JU, Schwarz M. Significance of CFTR gene mutations in patients with congenital aplasia of vas deferens with special regard to renal aplasia. Andrologia. 2012;44(5):305-7. doi: 10.1111/j.1439-0272.2012.01281.x.
  • 30. Gajbhiye R, Kadam K, Khole A, Gaikwad A, Kadam S, Shah R, et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene abnormalities in Indian males with congenital bilateral absence of vas deferens & renal anomalies. Indian J Med Res. 2016;143(5):616-23. doi: 10.4103/0971-5916.187110.
  • 31. Tuttelmann F, Simoni M, Kliesch S, Ledig S, Dworniczak B, Wieacker P, et al. Copy number variants in patients with severe oligozoospermia and Sertoli-cell-only syndrome. PloS one. 2011;6(4):e19426. doi: 10.1371/journal.pone.0019426.
  • 32. Halder A, Kumar P, Jain M, Iyer VK. Copy number variations in testicular maturation arrest. Andrology. 2017;5(3):460-72. doi: 10.1111/andr.12330.
  • 33. Yasin H, Gibson WT, Langlois S, Stowe RM, Tsang ES, Lee L, et al. A distinct neurodevelopmental syndrome with intellectual disability, autism spectrum disorder, characteristic facies, and macrocephaly is caused by defects in CHD8. J Hum Genet. 2019;64(4):271-80. doi: 10.1038/s10038-019-0561-0.
  • 34. Kamnasaran D, Cox DW. Current status of human chromosome 14. Journal of medical genetics. 2002;39(2):81-90. doi: 10.1136/jmg.39.2.81.
  • 35. Rockett JC, Mapp FL, Garges JB, Luft JC, Mori C, Dix DJ. Effects of hyperthermia on spermatogenesis, apoptosis, gene expression, and fertility in adult male mice. Biol Reprod. 2001;65(1):229-39. doi: 10.1095/biolreprod65.1.229.
  • 36. Bansal SK, Gupta N, Sankhwar SN, Rajender S. Differential Genes Expression between Fertile and Infertile Spermatozoa Revealed by Transcriptome Analysis. PloS one. 2015;10(5):e0127007. doi: 10.1371/journal.pone.0127007.
  • 37. Li CY, Jiang LY, Chen WY, Li K, Sheng HQ, Ni Y, et al. CFTR is essential for sperm fertilizing capacity and is correlated with sperm quality in humans. Human reproduction. 2010;25(2):317-27. doi: 10.1093/humrep/dep406.
  • 38. Flannigan R, Schlegel PN. Genetic diagnostics of male infertility in clinical practice. Best Pract Res Clin Obstet Gynaecol. 2017;44:26-37. doi: 10.1016/j.bpobgyn.2017.05.002.
Toplam 38 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Klinik Tıp Bilimleri
Bölüm Araştırma Makalesi
Yazarlar

Durkadın Demir Ekşi 0000-0002-5887-3141

Elanur Yılmaz Bu kişi benim 0000-0001-7045-5068

Yiğit Akın 0000-0001-7627-3476

Mustafa Faruk Usta Bu kişi benim 0000-0001-6402-3269

Mehmet Murad Başar Bu kişi benim 0000-0002-4732-1923

Semra Kahraman Bu kişi benim 0000-0002-2686-4240

Munire Erman 0000-0002-3856-3787

Özgül M. Alper Bu kişi benim 0000-0003-1536-2111

Proje Numarası SBAG-115S171
Yayımlanma Tarihi 30 Ağustos 2021
Gönderilme Tarihi 10 Temmuz 2021
Kabul Tarihi 1 Ağustos 2021
Yayımlandığı Sayı Yıl 2021 Cilt: 5 Sayı: 2

Kaynak Göster

Vancouver Demir Ekşi D, Yılmaz E, Akın Y, Usta MF, Başar MM, Kahraman S, Erman M, Alper ÖM. Copy Number Variation Analysis in Turkish Patients with Congenital Bilateral Absence of Vas Deferens. Acta Med. Alanya. 2021;5(2):181-9.

9705 

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