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Importance of Structural Abnormalities Detected by Array-Comparative Genomic Hybridization in Recurrent Miscarriage: A retrospective Study

Yıl 2023, Cilt: 7 Sayı: 3, 631 - 639, 30.09.2023
https://doi.org/10.46237/amusbfd.1330660

Öz

Objective: Chromosomal anomalies are among the most important risk factors of recurrent miscarriage. In 5.5% of the cases, one of the parents has cytogenetic anomaly in contrast to 0.55% of the general population. Recent literature data have used a‐CGH for detection of cause of abortion, but there are few studies specifically conducted to evaluate the correlation of chromosomal rearrangement and recurrent miscarriages; yet there is no clear evidence on this issue. In this study, we aimed on the correlation of chromosomal rearrangement in couples with unexplained recurrent miscarriage by a-CGH.
Methods: The karyotyping and aCGH data of 74 patients with more than five abortions were analyzed retrospectively. Cell cultures, harvesting, and G-banding at the level of 400-550 bands for karyotyping were performed following standardized procedures. The extracted maternal or paternal DNA concentration and quality were measured with the spectrophotometer and gel electrophoresis, respectively.
Results: A total of 74 patients, 50 women with male partners of 24 were included in the study. The results of a-CGH were normal for 22 males (91.7%) and 46 females (92%) and the distribution of the normal patients were not significant between the genders when patients with duplication and deletion anomalies (Duplication: 4q12, 2(p15-p14), 17q12; Deletion: 1(q21.1-q21.2), 16p11.2, Xp22.31) were compared (p > 0.05).
Conclusion: The maternal and paternal aCGH analysis yielded low rate of duplication and deletion anomalies of the chromosomes. The clinical significance of the yielded abnormalities need to be evaluated for patient consultation.

Kaynakça

  • 1. National Collaborating Centre for Women's and Children's Health (2012). Ectopic Pregnancy and Miscarriage: Diagnosis and Initial Management in Early Pregnancy of Ectopic Pregnancy and Miscarriage. NICE Clinical Guidelines, 154, 23.
  • 2. Practice Committee of the American Society for Reproductive M. (2008). Definitions of infertility and recurrent pregnancy loss. Fertil Steril, 89(6), 1603.
  • 3. Stirrat G.M. (1990). Recurrent miscarriage. Lancet, 336(8716), 673-675.
  • 4. Rai R., & Regan L. (2006). Recurrent miscarriage. Lancet, 368(9535),601-611.
  • 5. Garcia-Enguidanos A., Calle M.E., Valero J., Luna S., & Dominguez-Rojas V. (2002). Risk factors in miscarriage: A review. Eur J Obstet Gynecol Reprod Biol, 102(2), 111-119.
  • 6. Alijotas-Reig J., & Garrido-Gimenez C. (2013). Current concepts and new trends in the diagnosis and management of recurrent miscarriage. Obstet Gynecol Surv, 68(6), 445-466.
  • 7. Sierra S, & Stephenson M.( 2006). Genetics of recurrent pregnancy loss. Semin Reprod Med, 24(1), 17-24.
  • 8. Practice Committee of the American Society for Reproductive M. (2012). Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril, 98(5), 1103-1111.
  • 9. Menasha J., Levy B., Hirschhorn K., & Kardon N.B.( 2005). Incidence and spectrum of chromosome abnormalities in spontaneous abortions: new insights from a 12-year study. Genet Med, 7(4), 251-263.
  • 10. Carp H., Feldman B., Oelsner G., & Schiff E.( 2004). Parental karyotype and subsequent live births in recurrent miscarriage. Fertil Steril, 81(5), 1296-1301.
  • 11. Nagaishi M., Yamamoto T., Iinuma K., Shimomura K., Berend S.A., & Knops J. (2004). Chromosome abnormalities identified in 347 spontaneous abortions collected in Japan. J Obstet Gynaecol Res, 30(3) ,237- 241.
  • 12. Hyde K.J., & Schust D.J. (2015). Genetic considerations in recurrent pregnancy loss. Cold Spring Harb Perspect Med, 5(3), a023119.
  • 13. Hu Y., Chen X., Chen L.L., Xu Z.F., Wang X., & Cui H.( 2006). Comparative genomic hybridization analysis of spontaneous abortion. Int J Gynaecol Obstet, 92(1), 52-57.
  • 14. Oostlander A.E., Meijer G.A., & Ylstra B. (2004). Microarray-based comparative genomic hybridization and its applications in human genetics. Clin Genet, 66(6), 488-495.
  • 15. Bagheri H., Mercier E., Qiao Y., Stephenson M.D., & Rajcan-Separovic E. (2015). Genomic characteristics of miscarriage copy number variants. Mol Hum Reprod, 21(8), 655-661.
  • 16. Dhillon R.K., Hillman S.C., Morris R.K., McMullan D., Williams D., Coomarasamy A. et al. (2014). Additional information from chromosomal microarray analysis (CMA) over conventional karyotyping when diagnosing chromosomal abnormalities in miscarriage: a systematic review and meta-analysis. BJOG, 121(1), 11-21.
  • 17. Donaghue C., Davies N., Ahn J.W., Thomas H., Ogilvie C.M., & Mann K. (2017). Efficient and cost-effective genetic analysis of products of conception and fetal tissues using a QF-PCR/array CGH strategy; five years of data. Mol Cytogenet, 10, 12.
  • 18. Ozawa N., Sago H., Matsuoka K., Maruyama T., Migita O., Aizu Y. et al. (2016). Cytogenetic analysis of spontaneously discharged products of conception by array-based comparative genomic hybridization. Springerplus, 5(1), 874.
  • 19. Wou K., Hyun Y., Chitayat D., Vlasschaert M., Chong K., Wasim S. et al. (2016). Analysis of tissue from products of conception and perinatal losses using QF-PCR and microarray: A three-year retrospective study resulting in an efficient protocol. Eur J Med Genet, 59(8), 417-424.
  • 20. Sudhir N., Kaur T., Beri A., & Kaur A. (2016). Cytogenetic analysis in couples with recurrent miscarriages: a retrospective study from Punjab, north India. J Genet, 95(4), 887-894.
  • 21. De Krom G., Arens Y.H., Coonen E., Van Ravenswaaij-Arts C.M., Meijer-Hoogeveen M., Evers J.L. et al. (2015). Recurrent miscarriage in translocation carriers: no differences in clinical characteristics between couples who accept and couples who decline PGD. Hum Reprod, 30(2), 484-489.
  • 22. Najafi K., Gholami S., Moshtagh A., Bazrgar M., Sadatian N., Abbasi G. et al. (2019). Chromosomal aberrations in pregnancy and fetal loss: Insight on the effect of consanguinity, review of 1625 cases. Mol Genet Genomic Med, 7(8), e820.
  • 23. Moorhead P.S., Nowell P.C., Mellman W.J., Battips D.M., & Hungerford D.A. (1960). Chromosome preparations of leukocytes cultured from human peripheral blood. Exp Cell Res, 20, 613-616.
  • 24. Chen C.P., Su Y.N., Chen Y.T., Chen W.L., Hsu L.J., & Wang W. (2011). Prenatal diagnosis of directly transmitted benign 4q12-q13.1 quadruplication associated with tandem segmental amplifications of the LPHN3 gene. Taiwan J Obstet Gynecol, 50(3), 401-404.
  • 25. Kasnauskiene J., Cimbalistiene L., Utkus A., Ciuladaite Z., Preiksaitiene E., Peciulyte A. et al. (2013). Two new de novo interstitial duplications covering 2p14-p22.1: clinical and molecular analysis. Cytogenet Genome Res, 139(1), 52-58.
  • 26. Brisset S., Capri Y., Briand-Suleau A., Tosca L., Gras D., Fauret-Amsellem A.L. et al. (2015). Inherited 1q21.1q21.2 duplication and 16p11.2 deletion: a two-hit case with more severe clinical manifestations. Eur J Med Genet, 58(9), 497-501.
  • 27. Hung C., Ayabe R.I., Wang C., Frausto R.F., Aldave A.J. (2013). Pre-Descemet corneal dystrophy and X- linked ichthyosis associated with deletion of Xp22.31 containing the STS gene. Cornea, 32(9), 1283-1287.
  • 28. Carrascosa-Romero M.C., Suela J., Alfaro-Ponce B., Cepillo-Boluda A.J. (2012). [X-chromosome-linked ichthyosis associated to epilepsy, hyperactivity, autism and mental retardation, due to the Xp22.31 microdeletion]. Rev Neurol, 54(4), 241-248.
  • 29. Ben Khelifa H., Soyah N., Ben-Abdallah-Bouhjar I., Gritly R., Sanlaville D., Elghezal H. et al. (2013). Xp22.3 interstitial deletion: a recognizable chromosomal abnormality encompassing VCX3A and STS genes in a patient with X-linked ichthyosis and mental retardation. Gene, 527(2), 578-583.
  • 30. Malla T.M., Pandith A.A., Dar F.A., Zargar M.H., Shah Z.A. (2014). De novo Xp terminal deletion in a triple X female with recurrent spontaneous abortions: a case report. J Genet, 93(3), 819-822.
  • 31. Li R., Fu F., Zhang Y.L., Li D.Z., Liao C. (2014). Prenatal diagnosis of 17q12 duplication and deletion syndrome in two fetuses with congenital anomalies. Taiwan J Obstet Gynecol, 53(4), 579-582.
  • 32. Rasmussen M., Vestergaard E.M., Graakjaer J., Petkov Y., Bache I., Fagerberg C. et al. (2016). 17q12 deletion and duplication syndrome in Denmark-A clinical cohort of 38 patients and review of the literature. Am J Med Genet A, 170(11),2934-2942.
  • 33. Daniely M., Aviram-Goldring A., Barkai G., & Goldman B. (1998). Detection of chromosomal aberration in fetuses arising from recurrent spontaneous abortion by comparative genomic hybridization. Hum Reprod, 13(4), 805-809.
  • 34. Barrett I.J., Lomax B.L., Loukianova T., Tang S.S., Lestou V.S., & Kalousek D.K. (2001). Comparative genomic hybridization: a new tool for reproductive pathology. Arch Pathol Lab Med, 125(1), 81-84.
  • 35. Bell K.A., Van Deerlin P.G., Haddad B.R., & Feinberg R.F. (1999). Cytogenetic diagnosis of "normal 46,XX" karyotypes in spontaneous abortions frequently may be misleading. Fertil Steril, 71(2), 334-341.
  • 36. Lomax B., Tang S., Separovic E., Phillips D., Hillard E., Thomson T. et al. (2000). Comparative genomic hybridization in combination with flow cytometry improves results of cytogenetic analysis of spontaneous abortions. Am J Hum Genet, 66(5), 1516-1521.
  • 37. Bell K.A., Van Deerlin P.G., Feinberg R.F., du Manoir S., & Haddad B.R. (2001). Diagnosis of aneuploidy in archival, paraffin-embedded pregnancy-loss tissues by comparative genomic hybridization. Fertil Steril, 75(2), 374-379.
  • 38. Colley E., Hamilton S., Smith P., Morgan N.V., Coomarasamy A., & Allen S. (2019). Potential genetic causes of miscarriage in euploid pregnancies: a systematic review. Hum Reprod Update, 25(4), 452-472.
  • 39. Schaeffer A.J., Chung J., Heretis K., Wong A., Ledbetter D.H., Lese Martin C. (2004). Comparative genomic hybridization-array analysis enhances the detection of aneuploidies and submicroscopic imbalances in spontaneous miscarriages. Am J Hum Genet, 74(6), 1168-1174.
  • 40. Jia Y., Zhao H., Shi D., Peng W., Xie L., Wang W. et al. (2014). Genetic effects of a 13q31.1 microdeletion detected by noninvasive prenatal testing (NIPT). Int J Clin Exp Pathol, 7(10), 7003-7011.

Tekrarlayan Düşüklerde Array Karşılaştırmalı Genomic Hibridizasyonun Yapısal Anomalileri Saptamadaki Önemi: Retrospektif Bir Çalışma

Yıl 2023, Cilt: 7 Sayı: 3, 631 - 639, 30.09.2023
https://doi.org/10.46237/amusbfd.1330660

Öz

Amaç: Kromozomal anomaliler, tekrarlayan düşüklerin en önemli risk faktörleri arasındadır. Vakaların %5.5'inde, ebeveynlerden birinin sitogenetik anormalliği mevcuttur ki bu oran genel nüfusa göre %0.55'tir. Son literatür verileri, düşüklere neden olan sebeplerin tespiti için a‐CGH yöntemini kullanmış olsa da, kromozomal yeniden düzenlemenin ve tekrarlayan düşüklerin korelasyonunu değerlendirmek için özel olarak yapılan az sayıda çalışma bulunmaktadır; ancak bu konuda net bir kanıt bulunmamaktadır. Bu çalışmada, a-CGH yöntemi kullanılarak açıklanamayan tekrarlayan düşükleri olan çiftlerde kromozomal yeniden düzenlenmenin korelasyonunu amaçladık.
Yöntem: Beşten fazla düşüğü olan 74 hastanın karyotipleme ve a-CGH verileri retrospektif olarak analiz edildi. Hücre kültürleri, karyotipleme için standartlaşmış prosedürler takiben 400-550 bant düzeyinde hücre hasadı ve G-bantlama işlemleri gerçekleştirildi. Anne veya baba DNA'sının ekstrakte edilen miktarı ve kalitesi sırasıyla spektrofotometre ve jel elektroforezi ile ölçüldü.
Bulgular: Toplam 74 hasta arasında, çalışmaya 50 kadın ve 24 erkek dahil edildi. A-CGH sonuçları, erkeklerin 22'sinde (%91.7) ve kadınların 46'sında (%92) normal olarak bulundu ve normal hastaların, duplikasyon ve delesyon anormallikleri (Duplikasyon: 4q12, 2(p15-p14), 17q12; Delesyon: 1(q21.1-q21.2), 16p11.2, Xp22.31) olan hastalarla karşılaştırıldığında dağılımı anlamlı değildi (P > 0.05).
Sonuç: Anne ve baba adaylarının kromozmlarının aCGH ile araştırılması sonucunda düşük oranda delesyon ve dublikasyon anormallikleri izlenmiştir. Hastalara gerekli danışmanlığın verilebilmesi için bu anormalliklerin klinik önemi araştırılmalıdır.

Kaynakça

  • 1. National Collaborating Centre for Women's and Children's Health (2012). Ectopic Pregnancy and Miscarriage: Diagnosis and Initial Management in Early Pregnancy of Ectopic Pregnancy and Miscarriage. NICE Clinical Guidelines, 154, 23.
  • 2. Practice Committee of the American Society for Reproductive M. (2008). Definitions of infertility and recurrent pregnancy loss. Fertil Steril, 89(6), 1603.
  • 3. Stirrat G.M. (1990). Recurrent miscarriage. Lancet, 336(8716), 673-675.
  • 4. Rai R., & Regan L. (2006). Recurrent miscarriage. Lancet, 368(9535),601-611.
  • 5. Garcia-Enguidanos A., Calle M.E., Valero J., Luna S., & Dominguez-Rojas V. (2002). Risk factors in miscarriage: A review. Eur J Obstet Gynecol Reprod Biol, 102(2), 111-119.
  • 6. Alijotas-Reig J., & Garrido-Gimenez C. (2013). Current concepts and new trends in the diagnosis and management of recurrent miscarriage. Obstet Gynecol Surv, 68(6), 445-466.
  • 7. Sierra S, & Stephenson M.( 2006). Genetics of recurrent pregnancy loss. Semin Reprod Med, 24(1), 17-24.
  • 8. Practice Committee of the American Society for Reproductive M. (2012). Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril, 98(5), 1103-1111.
  • 9. Menasha J., Levy B., Hirschhorn K., & Kardon N.B.( 2005). Incidence and spectrum of chromosome abnormalities in spontaneous abortions: new insights from a 12-year study. Genet Med, 7(4), 251-263.
  • 10. Carp H., Feldman B., Oelsner G., & Schiff E.( 2004). Parental karyotype and subsequent live births in recurrent miscarriage. Fertil Steril, 81(5), 1296-1301.
  • 11. Nagaishi M., Yamamoto T., Iinuma K., Shimomura K., Berend S.A., & Knops J. (2004). Chromosome abnormalities identified in 347 spontaneous abortions collected in Japan. J Obstet Gynaecol Res, 30(3) ,237- 241.
  • 12. Hyde K.J., & Schust D.J. (2015). Genetic considerations in recurrent pregnancy loss. Cold Spring Harb Perspect Med, 5(3), a023119.
  • 13. Hu Y., Chen X., Chen L.L., Xu Z.F., Wang X., & Cui H.( 2006). Comparative genomic hybridization analysis of spontaneous abortion. Int J Gynaecol Obstet, 92(1), 52-57.
  • 14. Oostlander A.E., Meijer G.A., & Ylstra B. (2004). Microarray-based comparative genomic hybridization and its applications in human genetics. Clin Genet, 66(6), 488-495.
  • 15. Bagheri H., Mercier E., Qiao Y., Stephenson M.D., & Rajcan-Separovic E. (2015). Genomic characteristics of miscarriage copy number variants. Mol Hum Reprod, 21(8), 655-661.
  • 16. Dhillon R.K., Hillman S.C., Morris R.K., McMullan D., Williams D., Coomarasamy A. et al. (2014). Additional information from chromosomal microarray analysis (CMA) over conventional karyotyping when diagnosing chromosomal abnormalities in miscarriage: a systematic review and meta-analysis. BJOG, 121(1), 11-21.
  • 17. Donaghue C., Davies N., Ahn J.W., Thomas H., Ogilvie C.M., & Mann K. (2017). Efficient and cost-effective genetic analysis of products of conception and fetal tissues using a QF-PCR/array CGH strategy; five years of data. Mol Cytogenet, 10, 12.
  • 18. Ozawa N., Sago H., Matsuoka K., Maruyama T., Migita O., Aizu Y. et al. (2016). Cytogenetic analysis of spontaneously discharged products of conception by array-based comparative genomic hybridization. Springerplus, 5(1), 874.
  • 19. Wou K., Hyun Y., Chitayat D., Vlasschaert M., Chong K., Wasim S. et al. (2016). Analysis of tissue from products of conception and perinatal losses using QF-PCR and microarray: A three-year retrospective study resulting in an efficient protocol. Eur J Med Genet, 59(8), 417-424.
  • 20. Sudhir N., Kaur T., Beri A., & Kaur A. (2016). Cytogenetic analysis in couples with recurrent miscarriages: a retrospective study from Punjab, north India. J Genet, 95(4), 887-894.
  • 21. De Krom G., Arens Y.H., Coonen E., Van Ravenswaaij-Arts C.M., Meijer-Hoogeveen M., Evers J.L. et al. (2015). Recurrent miscarriage in translocation carriers: no differences in clinical characteristics between couples who accept and couples who decline PGD. Hum Reprod, 30(2), 484-489.
  • 22. Najafi K., Gholami S., Moshtagh A., Bazrgar M., Sadatian N., Abbasi G. et al. (2019). Chromosomal aberrations in pregnancy and fetal loss: Insight on the effect of consanguinity, review of 1625 cases. Mol Genet Genomic Med, 7(8), e820.
  • 23. Moorhead P.S., Nowell P.C., Mellman W.J., Battips D.M., & Hungerford D.A. (1960). Chromosome preparations of leukocytes cultured from human peripheral blood. Exp Cell Res, 20, 613-616.
  • 24. Chen C.P., Su Y.N., Chen Y.T., Chen W.L., Hsu L.J., & Wang W. (2011). Prenatal diagnosis of directly transmitted benign 4q12-q13.1 quadruplication associated with tandem segmental amplifications of the LPHN3 gene. Taiwan J Obstet Gynecol, 50(3), 401-404.
  • 25. Kasnauskiene J., Cimbalistiene L., Utkus A., Ciuladaite Z., Preiksaitiene E., Peciulyte A. et al. (2013). Two new de novo interstitial duplications covering 2p14-p22.1: clinical and molecular analysis. Cytogenet Genome Res, 139(1), 52-58.
  • 26. Brisset S., Capri Y., Briand-Suleau A., Tosca L., Gras D., Fauret-Amsellem A.L. et al. (2015). Inherited 1q21.1q21.2 duplication and 16p11.2 deletion: a two-hit case with more severe clinical manifestations. Eur J Med Genet, 58(9), 497-501.
  • 27. Hung C., Ayabe R.I., Wang C., Frausto R.F., Aldave A.J. (2013). Pre-Descemet corneal dystrophy and X- linked ichthyosis associated with deletion of Xp22.31 containing the STS gene. Cornea, 32(9), 1283-1287.
  • 28. Carrascosa-Romero M.C., Suela J., Alfaro-Ponce B., Cepillo-Boluda A.J. (2012). [X-chromosome-linked ichthyosis associated to epilepsy, hyperactivity, autism and mental retardation, due to the Xp22.31 microdeletion]. Rev Neurol, 54(4), 241-248.
  • 29. Ben Khelifa H., Soyah N., Ben-Abdallah-Bouhjar I., Gritly R., Sanlaville D., Elghezal H. et al. (2013). Xp22.3 interstitial deletion: a recognizable chromosomal abnormality encompassing VCX3A and STS genes in a patient with X-linked ichthyosis and mental retardation. Gene, 527(2), 578-583.
  • 30. Malla T.M., Pandith A.A., Dar F.A., Zargar M.H., Shah Z.A. (2014). De novo Xp terminal deletion in a triple X female with recurrent spontaneous abortions: a case report. J Genet, 93(3), 819-822.
  • 31. Li R., Fu F., Zhang Y.L., Li D.Z., Liao C. (2014). Prenatal diagnosis of 17q12 duplication and deletion syndrome in two fetuses with congenital anomalies. Taiwan J Obstet Gynecol, 53(4), 579-582.
  • 32. Rasmussen M., Vestergaard E.M., Graakjaer J., Petkov Y., Bache I., Fagerberg C. et al. (2016). 17q12 deletion and duplication syndrome in Denmark-A clinical cohort of 38 patients and review of the literature. Am J Med Genet A, 170(11),2934-2942.
  • 33. Daniely M., Aviram-Goldring A., Barkai G., & Goldman B. (1998). Detection of chromosomal aberration in fetuses arising from recurrent spontaneous abortion by comparative genomic hybridization. Hum Reprod, 13(4), 805-809.
  • 34. Barrett I.J., Lomax B.L., Loukianova T., Tang S.S., Lestou V.S., & Kalousek D.K. (2001). Comparative genomic hybridization: a new tool for reproductive pathology. Arch Pathol Lab Med, 125(1), 81-84.
  • 35. Bell K.A., Van Deerlin P.G., Haddad B.R., & Feinberg R.F. (1999). Cytogenetic diagnosis of "normal 46,XX" karyotypes in spontaneous abortions frequently may be misleading. Fertil Steril, 71(2), 334-341.
  • 36. Lomax B., Tang S., Separovic E., Phillips D., Hillard E., Thomson T. et al. (2000). Comparative genomic hybridization in combination with flow cytometry improves results of cytogenetic analysis of spontaneous abortions. Am J Hum Genet, 66(5), 1516-1521.
  • 37. Bell K.A., Van Deerlin P.G., Feinberg R.F., du Manoir S., & Haddad B.R. (2001). Diagnosis of aneuploidy in archival, paraffin-embedded pregnancy-loss tissues by comparative genomic hybridization. Fertil Steril, 75(2), 374-379.
  • 38. Colley E., Hamilton S., Smith P., Morgan N.V., Coomarasamy A., & Allen S. (2019). Potential genetic causes of miscarriage in euploid pregnancies: a systematic review. Hum Reprod Update, 25(4), 452-472.
  • 39. Schaeffer A.J., Chung J., Heretis K., Wong A., Ledbetter D.H., Lese Martin C. (2004). Comparative genomic hybridization-array analysis enhances the detection of aneuploidies and submicroscopic imbalances in spontaneous miscarriages. Am J Hum Genet, 74(6), 1168-1174.
  • 40. Jia Y., Zhao H., Shi D., Peng W., Xie L., Wang W. et al. (2014). Genetic effects of a 13q31.1 microdeletion detected by noninvasive prenatal testing (NIPT). Int J Clin Exp Pathol, 7(10), 7003-7011.
Toplam 40 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Tıp Eğitimi
Bölüm Araştırma Makaleleri
Yazarlar

Bertan Akar 0000-0003-0494-6867

Emre Köle 0000-0002-4940-8862

Deniz Sünnetçi Akkoyunlu 0000-0001-9297-8222

Merve Çakır Köle 0000-0002-9330-3363

Naci Çine 0000-0001-9063-1073

Hakan Savlı 0000-0003-2836-9881

Eray Çalışkan 0000-0002-6799-5909

Erken Görünüm Tarihi 1 Ekim 2023
Yayımlanma Tarihi 30 Eylül 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 7 Sayı: 3

Kaynak Göster

APA Akar, B., Köle, E., Sünnetçi Akkoyunlu, D., Çakır Köle, M., vd. (2023). Tekrarlayan Düşüklerde Array Karşılaştırmalı Genomic Hibridizasyonun Yapısal Anomalileri Saptamadaki Önemi: Retrospektif Bir Çalışma. Adnan Menderes Üniversitesi Sağlık Bilimleri Fakültesi Dergisi, 7(3), 631-639. https://doi.org/10.46237/amusbfd.1330660