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DOI :10.26650/IUITFD.413596   IUP :10.26650/IUITFD.413596    Full Text (PDF)

APPLICATION OF MLPA (MULTIPLEX LIGATION-DEPENDENT PROBE AMPLIFICATION) IN FETUSES WITH AN ABNORMAL SONOGRAM AND NORMAL KARYOTYPE

Güven Toksoy, Birsen Karaman, Zehra Oya Uyguner, Kader Yılmaz, Recep Has, Hülya Kayserili Karabey, Peter Mıny, Seher Başaran

Objective/Material and Method: Cryptic chromosomal imbalances contribute significantly to the etiology of multiple congenital anomalies with or without mental retardation (MCA/MR). Current approaches in prenatal diagnosis include targeted high resolution analyses by MLPA and some microarray platforms or a genomewide screening at maximal resolution using oligonucleotide or SNP arrays. The major disadvantages of the latter approach are cost and the inadvertent detection of copy number variation of unknown clinical significance. In this prospective work, fetal DNA samples from 66 fetuses who had pathological antenatal ultrasonography findings with normal karyotype and Multiprobe T-FISH results were tested using commercially available targeted MLPA probe-sets to compare the efficacy and the impact of MLPA testing at prenatal setting. 

Results: Three submicroscopic deletions (3.66; 4.5%) were detected in the cohort. Two of them were de novo deletions, 18ptel and 7q11.23. The third finding was a 75 kb duplication at 18q, which was maternally inherited and probably a benign copy number variation unrelated to the pathological ultarsonography findings. 

Conclusion: The observed detection rate by MLPA testing can be considered within the expected range. Furthermore, benign copy number variation was identified with the targeted diagnostic approach as an unexpected finding. This study shows that MLPA is a practical and cost-effective technique to investigate submicroscobic chromosomal aberrations in fetuses. 
Keywords: MLPA, subtelomeric anomalies, prenatal diagnosis microdeletion/microduplication
DOI :10.26650/IUITFD.413596   IUP :10.26650/IUITFD.413596    Full Text (PDF)

NORMAL KARYOTİPLİ PATOLOJİK ULTRASON BULGUSU OLAN FETUSLARDA MLPA (MULTİPLEX LİGATİON-DEPENDENT PROBE AMPLİFİCATİON) UYGULAMALARI

Güven Toksoy, Birsen Karaman, Zehra Oya Uyguner, Kader Yılmaz, Recep Has, Hülya Kayserili Karabey, Peter Mıny, Seher Başaran

Amaç/Gereç/Yöntem: Multiple konjenital anomaliler ve bilişsel yetersizliklerin (MKA/MR) etiyolojisinde kriptik kromozom düzensizlikler önemli yer tutmaktadır. Yeni teknolojilerin gelişmesi, MLPA veya genom boyu SNP ve oligonükleotidlerle tarama yapabilen mikrodizin ya da yeni nesil dizileme teknolojileri yüksek düzeyde çözünürlükle bu anomalilerin prenatal dönemde saptanabilmesine olanak sağlamıştır. Yüksek çözünürlüklü çalışmaların en büyük dezavantajı maliyet ile beklenmeyen ve/veya klinik önemi bilinmeyen kopya sayısı varyantlarının saptanmasıdır. Bu prospektif çalışmada patolojik ultrason bulgusu saptanan ve normal karyotipe sahip çoklu telomerik FISH ile normal sonuç alınmış 66 fetusa ait DNA örnekleri ticari olarak satılan MLPA prob setleri ile değerlendirilerek MLPA nın tanı akış şemasındaki etkinliği araştırıldı. 

Bulgular: Çalışmada toplam üç olguda (3:66; 4,5%) delesyon belirlendi. İki olguda submikroskobik de novo delesyon saptandı ve bunlardan biri 18ptel ve diğeri 7q11.23 delesyonu idi. Bir diğer olguda klinik bulgularla ilişkisiz, yüksek olasılıkla zararsız 75 kb büyüklüğünde anneden kalıtılan 18q duplikasyonu belirlendi. 

Sonuç: Patojenik mutasyon saptama oranı beklenti ile uyumlu idi. Ek olarak, hedefe yönelik tanıda sıra dışı kabul edilen bir durum olarak bir olguda maternal kalıtımlı yüksek olasılıkla zararsız bir kopya sayısı değişikliği saptandı. Bu çalışma prenatal uygulamalarda submikroskobik kromozomal anomalilerin araştırılmasında MLPA tekniğinin uygun maliyetli ve kullanılabilir olduğunu göstermiştir. 
Keywords: MLPA, subtelomerik değişimler, doğum öncesi tanı mikrodelesyon/mikroduplikasyon

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APA

Toksoy, G., Karaman, B., Uyguner, Z.O., Yılmaz, K., Has, R., Kayserili Karabey, H., Mıny, P., & Başaran, S. (2019). APPLICATION OF MLPA (MULTIPLEX LIGATION-DEPENDENT PROBE AMPLIFICATION) IN FETUSES WITH AN ABNORMAL SONOGRAM AND NORMAL KARYOTYPE. Journal of Istanbul Faculty of Medicine, 82(1), 5-11. https://doi.org/10.26650/IUITFD.413596


AMA

Toksoy G, Karaman B, Uyguner Z O, Yılmaz K, Has R, Kayserili Karabey H, Mıny P, Başaran S. APPLICATION OF MLPA (MULTIPLEX LIGATION-DEPENDENT PROBE AMPLIFICATION) IN FETUSES WITH AN ABNORMAL SONOGRAM AND NORMAL KARYOTYPE. Journal of Istanbul Faculty of Medicine. 2019;82(1):5-11. https://doi.org/10.26650/IUITFD.413596


ABNT

Toksoy, G.; Karaman, B.; Uyguner, Z.O.; Yılmaz, K.; Has, R.; Kayserili Karabey, H.; Mıny, P.; Başaran, S. APPLICATION OF MLPA (MULTIPLEX LIGATION-DEPENDENT PROBE AMPLIFICATION) IN FETUSES WITH AN ABNORMAL SONOGRAM AND NORMAL KARYOTYPE. Journal of Istanbul Faculty of Medicine, [Publisher Location], v. 82, n. 1, p. 5-11, 2019.


Chicago: Author-Date Style

Toksoy, Güven, and Birsen Karaman and Zehra Oya Uyguner and Kader Yılmaz and Recep Has and Hülya Kayserili Karabey and Peter Mıny and Seher Başaran. 2019. “APPLICATION OF MLPA (MULTIPLEX LIGATION-DEPENDENT PROBE AMPLIFICATION) IN FETUSES WITH AN ABNORMAL SONOGRAM AND NORMAL KARYOTYPE.” Journal of Istanbul Faculty of Medicine 82, no. 1: 5-11. https://doi.org/10.26650/IUITFD.413596


Chicago: Humanities Style

Toksoy, Güven, and Birsen Karaman and Zehra Oya Uyguner and Kader Yılmaz and Recep Has and Hülya Kayserili Karabey and Peter Mıny and Seher Başaran. “APPLICATION OF MLPA (MULTIPLEX LIGATION-DEPENDENT PROBE AMPLIFICATION) IN FETUSES WITH AN ABNORMAL SONOGRAM AND NORMAL KARYOTYPE.” Journal of Istanbul Faculty of Medicine 82, no. 1 (Apr. 2024): 5-11. https://doi.org/10.26650/IUITFD.413596


Harvard: Australian Style

Toksoy, G & Karaman, B & Uyguner, ZO & Yılmaz, K & Has, R & Kayserili Karabey, H & Mıny, P & Başaran, S 2019, 'APPLICATION OF MLPA (MULTIPLEX LIGATION-DEPENDENT PROBE AMPLIFICATION) IN FETUSES WITH AN ABNORMAL SONOGRAM AND NORMAL KARYOTYPE', Journal of Istanbul Faculty of Medicine, vol. 82, no. 1, pp. 5-11, viewed 23 Apr. 2024, https://doi.org/10.26650/IUITFD.413596


Harvard: Author-Date Style

Toksoy, G. and Karaman, B. and Uyguner, Z.O. and Yılmaz, K. and Has, R. and Kayserili Karabey, H. and Mıny, P. and Başaran, S. (2019) ‘APPLICATION OF MLPA (MULTIPLEX LIGATION-DEPENDENT PROBE AMPLIFICATION) IN FETUSES WITH AN ABNORMAL SONOGRAM AND NORMAL KARYOTYPE’, Journal of Istanbul Faculty of Medicine, 82(1), pp. 5-11. https://doi.org/10.26650/IUITFD.413596 (23 Apr. 2024).


MLA

Toksoy, Güven, and Birsen Karaman and Zehra Oya Uyguner and Kader Yılmaz and Recep Has and Hülya Kayserili Karabey and Peter Mıny and Seher Başaran. “APPLICATION OF MLPA (MULTIPLEX LIGATION-DEPENDENT PROBE AMPLIFICATION) IN FETUSES WITH AN ABNORMAL SONOGRAM AND NORMAL KARYOTYPE.” Journal of Istanbul Faculty of Medicine, vol. 82, no. 1, 2019, pp. 5-11. [Database Container], https://doi.org/10.26650/IUITFD.413596


Vancouver

Toksoy G, Karaman B, Uyguner ZO, Yılmaz K, Has R, Kayserili Karabey H, Mıny P, Başaran S. APPLICATION OF MLPA (MULTIPLEX LIGATION-DEPENDENT PROBE AMPLIFICATION) IN FETUSES WITH AN ABNORMAL SONOGRAM AND NORMAL KARYOTYPE. Journal of Istanbul Faculty of Medicine [Internet]. 23 Apr. 2024 [cited 23 Apr. 2024];82(1):5-11. Available from: https://doi.org/10.26650/IUITFD.413596 doi: 10.26650/IUITFD.413596


ISNAD

Toksoy, Güven - Karaman, Birsen - Uyguner, ZehraOya - Yılmaz, Kader - Has, Recep - Kayserili Karabey, Hülya - Mıny, Peter - Başaran, Seher. “APPLICATION OF MLPA (MULTIPLEX LIGATION-DEPENDENT PROBE AMPLIFICATION) IN FETUSES WITH AN ABNORMAL SONOGRAM AND NORMAL KARYOTYPE”. Journal of Istanbul Faculty of Medicine 82/1 (Apr. 2024): 5-11. https://doi.org/10.26650/IUITFD.413596



TIMELINE


Submitted09.04.2018
Accepted08.10.2018
Published Online28.03.2019

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