RE-EVALUATION OF COPY NUMBER VARIATIONS IN NEUROPSYCHIATRIC DISORDERS

Öz

OBJECTIVE: Chromosome segment variations involving more than 50 bases are called Copy Number Variations (CNV). Chromosomal microarray method is used to detect CNVs in a routine practice. Chromosomal microarray analysis (CMA) is a first-tier test in the evaluation of individuals with intellectual disability and developmental delay with the diagnostic yield ranging from 5 to 20% varying based on population examined. The International Standard for the Consortium of Cytogenomic Array recommended CMA as a first-stage cytogenetic diagnostic test for patients with CA and ID / GDD. This study aimed to compare the standard and new high resolution analyze methods.
MATERIAL AND METHODS: Our study was carried out with retrospective evaluation of 500 patients with CMA with different indications with Affymetrix Cytoscan Optima chips in Ankara Atatürk Research and Education Hospital.
RESULTS: In the standard analysis method, 313 CNVs was detected at 298 patients. New analyze method detected 939 CNVs at 362 patients. Standard analysis method could not detect 3 pathogenic CNVs which were below 100-Kb. While in the standard analysis, 56 pathogenic CNVs was found in the new analysis method. The number of CNVs classified as unknown clinically was 105 in the standard method and 318 in the new analysis method. In addition, 12 CNVs with a frequency of more than 1% were detected in our study.
CONCLUSIONS: Although the new method has increased the diagnostic percentage of the test from 10.7 to 11.3, it increases the clinical significance and increases the false positive results. This has led to a higher sensitivity of the analysis, but has led to an increase in both the duration of the analysis and other results that can be called artifacts in the test. In addition, 10 CNVs which are relatively common in Turkish population have been reported in our study.
KEYWORDS: , 

Anahtar Kelimeler

• Microarray analysis
• Copy number varia
• Neuropsychiatric disorders

Proje Numarası

Yok

NÖROPSİKİYATRİK BOZUKLUĞU OLAN HASTALARDA KOPYA SAYISI DEĞİŞİKLİKLERİNİN YENİDEN DEĞERLENDİRİLMESİ

Öz

AMAÇ: İnsan genomunda bulunan 50 bazdan büyük değişikliklere ‘Kopya Sayısı Değişiklikleri’ (Copy Number Variations-CNV) adı verilmektedir. CNV’leri saptamak için rutinde mikrodizin (microarray) yöntemi kullanılmaktadır. Mikrodizin yöntemi zihinsel yetersizliğin, otizm spektrum bozukluğunun, çoklu doğumsal anomalilerin nedeninin saptanmasında ilk basamak testi olarak önerilmektedir. Çalışmanın amacı mikrodizin analizi ile saptanan değişikliklerin farklı filtreler ile değerlendirilip sonuçların karşılaştırılmasıdır.
GEREÇ VE YÖNTEM: Çalışmamız Sağlık Bakanlığı, Ankara Merkez Genetik Laboratuvarı bünyesinde farklı nöro-psikiyatrik bozukluk endikasyonlarla Affimetrix Cytoscan Optima çipleri ile mikrodizin yapılmış 500 hasta verisinin retrospektif değerlendirilmesi ile yapılmıştır. 500 hastanın verileri standart analiz yöntemi ile ve daha yüksek duyarlıkta analiz yapabilmek için 5 marker ve 1 kilobaz büyüklükteki değişiklikler incelenmiştir ve sonuçlar karşılaştırılmıştır.
BULGULAR: Standart analiz metodunda CNV saptanan 249 hastadan toplamda 313 CNV (%1.25) bulunmuş, daha yüksek çözünürlüklü analizde 362 hastadan 939 (%2.6) CNV tespit edilmiştir. Standart analizde 53 CNV saptanırken, yeni analiz metodunda 56 CNV saptanmıştır. Klinik anlamı bilinmeyen olarak sınıflanan CNV sayısı Standart yöntemde 105 iken, önerdiğimiz yeni analiz metodunda 318 olarak tespit edilmiştir. Ayrıca çalışmamız sırasında toplum frekansı %1’den büyük olan 12 CNV tespit edilmiştir.
SONUÇ: Sonuç olarak yeni yöntem testin tanı verme yüzdesini 10.7’den 11.3’e çıkarmış olmakla birlikte, klinik anlamı bilinmeyen ve olası yanlış pozitif sonuçları arttırmaktadır. Bu da analizi daha yüksek duyarlılıkla yapmakla birlikte, hem analiz süresini hem de testteki artefakt olarak adlandırılabilecek diğer sonuçların artmasına neden olmuştur. Ayrıca çalışmamızda Türk toplumunda göreceli olarak sık görülen 12 adet CNV bildirilmiştir.

Anahtar Kelimeler

• KOPYA SAYISI DEĞİŞİKLİKLERİ
• NÖROPSİKİYATRİK BOZUKLUK
• Mikrodizin analizi

Destekleyen Kurum

Yok

Proje Numarası

Yok

Teşekkür

Yok

Kaynakça

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