Turkiye Klinikleri Journal of Medical Sciences

.: ORIGINAL RESEARCH
Kardiyak Anomalili Fetüslerde Kromozomal Mikrodizin Analizinin Tanıdaki Etkinliği: Kohort Araştırması
The Effectiveness of Chromosomal Microarray Analysis in Diagnosis of Fetuses with Cardiac Anomalies: Cohort Research
Hilal ŞENTÜRKa,b, Bilge ÖZSAİT SELÇUKa , Tuğba SARAÇ SİVRİKOZc , Tuğba KALAYCIa , Rukiye Nurten ÖMEROĞLUd , Gülnihal BULUTa,b, İbrahim H. KALELİOĞLUc , Recep HASc , Atıl YÜKSELc , Seher BAŞARANa , Birsen KARAMAN a,e, Evrim KÖMÜRCÜ BAYRAKa
aİstanbul Üniversitesi İstanbul Tıp Fakültesi, Tıbbi Genetik ABD, İstanbul, Türkiye
bİstanbul Üniversitesi Sağlık Bilimleri Enstitüsü, İstanbul, Türkiye
cİstanbul Üniversitesi İstanbul Tıp Fakültesi, Kadın Hastalıkları ve Doğum ABD, Perinatoloji BD, İstanbul, Türkiye
dİstanbul Üniversitesi İstanbul Tıp Fakültesi, Çocuk Sağlığı ve Hastalıkları ABD, İstanbul, Türkiye
eİstanbul Üniversitesi Çocuk Sağlığı Enstitüsü, Pediatrik Temel Bilimleri ABD, İstanbul, Türkiye
Turkiye Klinikleri J Med Sci. 2023;43(3):302-13
doi: 10.5336/medsci.2022-94687
Article Language: TR
Full Text
ÖZET
 Amaç: Bu çalışmada, fetal olgularda konjenital kalp anomalileri (KKA) sıklığı, malformasyonun tipi/dağılımı ve sitogenetik ve moleküler sitogenetik tanı yöntemlerinin KKA'nın prenatal tanısındaki etkinliğinin araştırılması amaçlandı. Gereç ve Yöntemler: 2014-2021 yılları arasında, fetal ultrasonografide (USG) çeşitli patolojiler sebebiyle karyotip analizi, 22q11.2 delesyon sendromuna özgü prob kullanılarak (N25/D22S75, ARSA, Aquarius-Cytocell) floresan in-situ hibridizasyon [fluorescence in-situ hybridization (FISH)] incelemesi ve kromozomal mikrodizin (KMD) çalışması yapılan 951 fetal olgu arasında KKA saptanan 192'si bu çalışmada değerlendirildi. Olguların fetal hücrelerinden genomik DNA izolasyonu kit protokolüne göre (MagNA Pure LC DNA İzolasyon Kiti I) yapılarak KMD (180K, Agilent SurePrint G3 Hmn CGH+SNP) uygulandı. Bulgular: KKA'lı 192 fetal olgunun soy geçmişlerinde, kardiyak anomaliler için gebelik öyküsü veya 1. derece akrabalarında benzer patolojik bulguların varlığı %9,9 oranında saptandı. KKA'lı olguların 23'üne konvansiyonel sitogenetik ve moleküler sitogenetik yöntemleriyle tanı konuldu (23/192, %12). Olguların 11'i karyotip ve KMD (11/23, %47,8), 3 olguda (3/23, %13) FISH incelemesi, 9 olguda ise (9/23, %39,1) KMD analizi ile anomali saptandı. Genetik tanı alan olgular, birden fazla kardiyak anomali (kompleks) ve/veya diğer organ tutulumlarına sahipti. Bu teknikler ile herhangi bir patoloji saptanmayan 169 olgunun 21'inde (%12,4) USG'de tek bir kardiyak anomali (izole) saptanırken, kompleks kardiyak anomalisi olan olgu sayısı 44 (%26) idi. Yüz dört olguda ise (%61,5), kardiyak anomalinin yanı sıra minör/majör multisistemik tutulumlar mevcuttu. Sonuç: KKA'lı olguların erken prenatal tanısı, gebelik sürecinin yönetimi ve genetik danışmada önem taşımaktadır. Bu çalışmada, fetal USG'de KKA saptanan olgularda (izole, kompleks, multisistemik tutulumlu) genetik etiyolojisinin aydınlatılmasına diğer sitogenetik teknikleri ile birlikte KMD analizinin katkısı %12 olarak bulundu. USG'de izole kardiyak bulgu olsa dahi tüm KKA'lı olgulara KMD analizi önerilebilir.

Anahtar Kelimeler: Konjenital kalp anomalileri; kromozomal mikrodizin; karyotip; floresan in-situ hibridizasyon
ABSTRACT
 Objective: In this study, we aimed to investigate the frequency of congenital heart anomalies (CHA), the type/distribution of malformations and the effectiveness of conventional genetic diagnosis methods in the prenatal diagnosis of CHA in fetal cases. Material and Methods: In this study, CHA was detected in 192 of 951 cases in which karyotype analysis, fluorescence in-situ hybridization (FISH) examination using 22q11.2 deletion syndrome specific probe (N25/D22S75, ARSA, Aquarius-Cytocell) and chromosomal microarray (CMA) study were performed due to various pathologies in fetal ultrasonography (USG) between 2014 and 2021. Genomic DNA isolation from fetal cells of the cases was performed according to the kit protocol (MagNA Pure LC DNA Isolation Kit I) and CMA (180K, Agilent SurePrint G3 Hmn CGH+SNP) was performed. Results: In the family history of 192 fetal cases with CHA, pregnancy history for cardiac anomalies or presence of similar pathological findings in their first degree relatives was found in 9.9%. Twenty-three of the CHA cases were diagnosed by conventional cytogenetic and molecular cytogenetic methods (23/192, 12%). Anomaly was detected by karyotyping and CMA in 11 cases (11/23, 47.8%), by FISH in 3 cases (3/23, 13%), and by CMA analysis in 9 cases (9/23, 39.1%). The cases with genetic diagnosis had more than one cardiac anomaly (complex) and/or other organ involvement. Of the 169 cases whose pathology was not detected by these techniques, a single heart anomaly (isolated) was detected on USG in 21 of them (12.4%) and complex heart anomaly was found in 44 of them (26%). In 104 cases (61.5%), there were minor/major multisystemic involvements as well as cardiac anomaly. Conclusion: Early prenatal diagnosis of CHA cases is important in the management of pregnancy process and genetic counseling. In this study, the contribution of CMA analysis in combination with other cytogenetic techniques to elucidate the genetic etiology of cases (isolated, complex, multisystemic involvement) with CHA was determined as 12%. CMA analysis can be recommended for all patients with CHA, even if there is isolated cardiac finding on USG.

Keywords: Congenital heart anomalies; chromosomal microarray; karyotype; fluorescence in-situ hybridization
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