Kromozomal Mikroarray ve Tıpta Kullanımı
Özet
Kromozomal mikroarray (KMA) tekniği, bütün kromozomlar boyunca dağılmış moleküler belirteçleri kullanarak submikroskobik delesyon, duplikasyon ve dengesiz yeniden düzenlenmeleri belirleyen üstün bir moleküler karyotipleme metodudur. Geleneksel G bantlama yöntemi ancak 5-10 Mb büyüklüğündeki anomalileri saptayabilirken, KMA kilobaz aralığındaki kopya sayısı varyasyonlarını (CNV) başarıyla tespit eder. Günümüzde prenatal ve postnatal genetik tanıda yaygınlaşan bu teknoloji, özellikle aCGH ve SNP array olmak üzere iki temel yaklaşımla uygulanmaktadır. KMA; otizm spektrum bozukluğu, gelişme geriliği, entelektüel yetersizlik, çoklu konjenital anomaliler ve ultrasonografide yapısal anomali saptanan fetuslar için kılavuzlarda birinci basamak klinik test olarak önerilmektedir. Yapılan geniş kapsamlı prenatal çalışmalar, USG anomalisi olan fetuslarda KMA’nın patojenik bulguları saptama oranını %6-7 artırdığını göstermektedir. Postnatal dönemde ise geleneksel yöntemlerin %3-5 olan başarı oranına karşılık, KMA nörogelişimsel bozukluğu olan çocukların %15-20'sinde etiyolojiyi aydınlatabilmektedir. Hücre kültürüne ihtiyaç duymadan doğrudan DNA'dan hızlı sonuç veren bu yöntem, dengeli kromozomal translokasyonları ve nokta mutasyonlarını ise saptayamamaktadır.
Chromosomal microarray (CMA) technique is an advanced molecular karyotyping method that detects submicroscopic deletions, duplications, and unbalanced rearrangements using molecular markers distributed across all chromosomes. While conventional G-banding can only capture anomalies of 5-10 Mb in size, CMA successfully identifies copy number variations (CNVs) in the kilobase range. Increasingly integrated into prenatal and postnatal genetic diagnosis, this technology is utilized through two main platforms: aCGH and SNP array. CMA is recommended as a first-tier clinical test in guidelines for children with autism spectrum disorder, developmental delay, intellectual disability, multiple congenital anomalies, and fetuses presenting with structural abnormalities on ultrasonography. Comprehensive prenatal studies demonstrate that CMA increases the detection rate of pathogenic findings by 6-7% in fetuses with ultrasound anomalies. Postnatally, whereas traditional methods yield a success rate of only 3-5%, CMA elucidates the etiology in 15-20% of children with neurodevelopmental disorders. This method provides rapid results directly from isolated DNA without requiring cell culture; however, it cannot detect balanced chromosomal translocations and point mutations.
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