Bertan AKAR, Emre KÖLE, Deniz SÜNNETÇİ AKKOYUNLU, Merve ÇAKIR KÖLE, Naci ÇİNE, Hakan SAVLI, Eray ÇALIŞKAN

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

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.

Anahtar Kelimeler:

Dizi Karşılaştırmalı Genomik Hibridizasyon, Tekrarlayan Düşük, Kromozomal Anomaliler, Kromozomal Duplikasyon, Kromozomal Delesyon

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

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.

Keywords:

Array-Comparative Genomic Hybridization, Recurrent Miscarriage, Chromosomal Anomalies, Chromosomal Duplication, Chromosomal Deletion,

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