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Serebral Kavernöz Malformasyonların Moleküler ve Genetik Temelleri

Molecular and Genetic Basis of Cerebral Cavernous Malformations

Journal Name:

Publication Year:

DOI: 
10.17954/amj.2017.64

Keywords (Original Language):

Abstract (2. Language): 
Objective: Cerebral Cavernous Malformations (CCM) are vascular lesions that can cause potentially lethal focal neurologic problems and hemorrhagic stroke. Loss of function mutations in the relevant genes emerge sporadically or with familial inheritance. Material and Methods: The aim of the study was to determine the molecular and genetic basis of CCMs and their known roles in cells. Results: Genetic studies have so far suggested that three genes are associated with the pathogenesis of CCM; KRIT1 (KREV1 - RAP1A interaction trapped-1 or CCM1), CCM2 (OSM or Osmo-sensing scaffold for MEKK3) and PDCD10 (Programmed cell death 10 or CCM3). The encoded proteins of these genes form a triple complex in addition to their solitary roles. These genes encode proteins that are involved in cell junction, cell-cell adhesion, cell migration and apoptosis. The problems that develop in the vascular endothelium have serious effects, especially in the central nervous system. Conclusion: CCM genes will provide more information on their role in the cell junction, cell death and migration in the future.
Abstract (Original Language): 
Amaç: Serebral kavernöz malformasyonlar (SKM) santral sinir sisteminde ölümcül hemorajik inmelere ve fokal nörolojik sorunlara neden olma eğilimi gösteren damarsal lezyonlardır. Bu malformasyonlar, ilgili genlerinden birisinde oluşacak fonksiyon kaybı mutasyonlarıyla ortaya çıkmakta olup; büyük çoğunlukta sporadik olmasına rağmen ailesel kalıtımla da ortaya çıktığı genetik çalışmaların sonuçlarıyla da belirtilmektedir. Gereç ve Yöntemler: SKM ve ilgili genlerin moleküler ve genetik özelliklerini değerlendirerek hastalığın mekanizmalarının aydınlatılmaya çalışılması amaçlanmaktadır. Bulgular: İnsan üzerinde yapılan genetik çalışmalar bu hastalığın üç gen bölgesi ile bağlantısı olduğunu göstermiş; bunlar; KRIT1 (KREV1 - RAP1A interaction trapped-1 veya CCM1), CCM2 (OSM veya Osmo-sensing scaffold for MEKK3) ve PDCD10 (Programmed cell death 10 veya CCM3) genleri olarak belirlenmiştir. Bu genlerin eksprese ettikleri proteinler, tek başlarına işlev sahibi olmalarının yanında birlikte görev aldıkları üçlü kombine yapılarıyla da hücre-hücre bağlantılarında, hücrenin migrasyonu ve apoptozunda önemli görevleri üstlenmektedirler. Özellikle endotel hücrelerinde ortaya çıkan bu sorunlar merkezi sinir sisteminde ciddi etkilerle kendini göstermektedir. Sonuç: SKM ile ilişkili genler ve proteinlerin görevlerinin detaylı olarak aydınlatılması, birçok hastalığın temelinde de etkin rol oynayabileceği fikrini desteklemektedir. Özellikle hücre-hücre bağlantıları, hücrenin migrasyonu ve ölümü gibi önemli basamakların işlemesindeki rolleri, bu proteinlerin önemini anlamamıza olanak sağlayacak ve konuyla ilgili literatürün gelişmesine ışık tutacaktır.
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