Clinical utility of next-generation sequencing in neurodevelopmental disorders: non-syndromic intellectual disability as a model

Öz

Intellectual disability (ID) refers to a diverse group of disorders with marked heterogeneity in both clinical presentation and genetic etiology. Some cases of ID are associated with distinctive clinical findings that can lead to specific clinical and molecular diagnoses. However, sporadic cases of ID also occur in which the molecular pathogenesis cannot be identified via clinical diagnosis, and the genetic etiology is often unknown. New genomic technologies such as whole-exome sequencing, in which selective sequencing of all protein-coding genomic regions is performed, have proved to be the most efficient and cost-effective approach for identifying disease-causing variants in neurodevelopmental disorders, even in small nuclear families. Successful gene discovery efforts will lead to an improved understanding of the cellular and molecular mechanisms underpinning cases of individuals diagnosed with neurodevelopmental disorders, will inform screening programs and will promote the development of novel and more effective pharmacotherapies of personalized approaches to medical management.

Keywords: Intellectual disability; next-generation sequencing; novel gene identification.

Anahtar Kelimeler

• Intellectual disability; next-generation sequencing; novel gene identification

Nörogelişimsel hastalıklarda yeni nesil dizilemenin klinik kullanımı: Model olarak sendromik olmayan zeka geriliği

Öz

Zeka geriliği hem klinik hem de genetik etyoloji olarak çeşitlilik gösteren geniş bir hastalık grubunu içerir. Zeka geriliği olan bazı hastalar spesifik klinik ve moleküler tanı konulmasına yardımcı olabilecek hastalığa özgü klinik bulgular gösterir. Bu tür özel klinik bulgular ile birlikte seyretmeyen zeka geriliğinde ise moleküler bozukluk klinik tanı ile ayırt edilemez ve genetik etyoloji sıklıkla bilinmemektedir. Tüm ekzom dizileme gibi genomun protein kodlayan tüm bölgelerinin dizilenmesini sağlayan yeni nesil genomik teknolojiler, nörogelişimsel hastalıklarda, çekirdek ailelerde bile hastalık nedeni olan mutasyonların bulunmasında en verimli ve uygun maliyetli yöntem olduklarını kanıtlamışlardır. Başarılı gen keşfi çalışmaları nörogelişimsel hastalıklı bireylerde altta yatan hücresel ve moleküler mekanizmaların anlaşılmasına yardımcı olacak, tarama programlarına bilgi aktaracak ve hastaların tıbbi bakımlarında hastaya özgü yeni ve daha etkili ilaç tedavilerine olanak sağlayacaktır

Anahtar Kelimeler

• Zeka geriliği; yeni nesil dizileme; yeni gen tespiti

Kaynakça

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