Determination of Copy Number Variations in Non-Syndromic Congenital Cleft Palate - Lip Patients

Öz

Cleft lip and palate is the most common craniofacial anomaly. There is no concomitant anomaly in 70% of the cases and it is called non-syndromic cleft lip and palate. Molecular and quantitative developments in the science of genetics suggest that genetic mechanisms may play a role in both syndromic and non-syndromic types of this pathology. Non-syndromic cleft lip / palate is a common developmental abnormality that occurs during the embryonic period. This study aims to define genetic abnormalities due to copy number changes in cleft lip / palate pathogenesis. Our study, using the CytoScan 180K sequence targeted to detect genome-wide copy number variations, was performed with a sample of 17 patients with cleft lip and palate aged 1-15 years. Seven significant copy number changes were detected. These changes consisted of duplications (9p23-p24, 18q12.1, Xp22.12, Xp22.31, Yq11.21 / 16q24.1) and deletions (5q21.3 and 6p22.3-23) in patients with cleft lip and palate. It has also been shown in our study that genetic factors play a role in non-syndromic cases. Larger scale genome screening studies continue in different populations as well. The important point to be kept in mind in prospective patient management is this; If there is a cleft lip and palate in the family and relatives, the risk of cleft lip and palate increases in the next child. Even in sporadic cases where parents are not affected, it should be kept in mind that the risk of oral cleft in the next child is increased and the family should be informed about the next pregnancy.

Anahtar Kelimeler

• Nonsyndromic cleft lip and palate
• genetic diagnosis
• a-CGH
• copy number variations

Sendromik Olmayan Konjenital Yarık Damak-Dudak Bulunan Hastalarda Kopya Sayısı Varyasyonlarının Belirlenmesi

Öz

Dudak damak yarığı en sık görülen kraniyofasiyal anomalidir. Olguların %70 inde eşlik eden anomali bulunmaz ve non sendromik dudak damak yarığı olarak adlandırılır. Genetik biliminde moleküler ve kantitatif olarak meydana gelen gelişmeler bu patolojinin sendromik ve sendromik olmayan her iki tipinde de genetik mekanizmalarının rol oynuyor olabileceğini düşündürmektedir. Sendromik olmayan yarık dudak/damak, embriyonik dönemde gerçekleşen yaygın bir gelişimsel anormalliktir. Bu çalışma, yarık dudak/damak patogenezinde yer alan kopya sayısı değişimlerine bağlı genetik anormallikleri tanımlamak amacı taşımaktadır. Genom çapında kopya sayısı varyasyonlarını saptama hedefli CytoScan 180K dizisi kullanılarak yaptığımız çalışma, 1-15 yaşları arasındaki 17 yarık damak dudak olan hasta örneği ile gerçekleştirilmiştir. Yedi önemli kopya sayısı değişimi saptanmıştır. Bu değişimler yarık damak dudak hastalarında, duplikasyonlardan (9p23-p24, 18q12.1, Xp22.12, Xp22.31, Yq11.21/16q24.1) ve delesyonlardan (5q21.3 ve 6p22.3-23) oluşuyordu. Genetik faktörlerin sendromik olmayan vakalarda da rol oynadığı çalışmamız ile de gösterilmiştir. Daha geniş ölçekli genom tarama çalışmaları farklı populasyonlarda da devam etmektedir. İleriye yönelik hasta yönetiminde göz önünde tutulması gereken; aile ve akrabalarda yarık dudak ve damak bulunması halinde sonraki çocukta yarık damak dudak görülme riskinin arttığıdır. Anne babanın etkilenmediği sporadik vakalarda dahi, bir sonraki çocukta oral yarık riskinin arttığı göz önünde tutulmalı ve aile, sonraki gebelik için mutlaka bilgilendirilmelidir.

Anahtar Kelimeler

• Nonsendromik yarık damak ve dudak
• genetik tanı
• a-CGH
• kopya sayısı değişimleri

Kaynakça

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