Molecular Genetic Diagnosis by Whole Exome Sequencing in Inherited Thrombocytopenia and Identification of New Responsible Genes
Project no. 21027 · Status: Kapanmış (Yayın bekleniyor) · 2020
Summary
<p>Inherited Thrombocytopenia (IT) consist of a very rare group of genetic diseases that lead to decreased number or dysfunction of platelets. Platelets play a role in the first stage in stopping bleeding, and mainly skin and mucosal bleeding can be observed in IT. However, in this group of diseases, besides bleeding, a wide variety of clinical findings can be seen. Some HPD is associated with disorders that predispose to familial myelodysplastic syndrome (MDS) and acute myeloblastic leukemia (AML). Early recognition of these diseases can improve prognosis with rapidly planned treatments.</p><p>While laboratory and first-line laboratory tests are usually sufficient to make a definitive diagnosis, clinical findings of IT may vary widely and it is often not possible to reach a definitive diagnosis without genetic tests. Considering both the difficulty of clinical differentiation and genetic heterogeneity of rare IT, it is an important problem to analyze individual genes that may be responsible.</p><p> </p><p>At the beginning of our project; to bring a holistic diagnostic approach to IT with the participation of pediatric hematologists, pediatric geneticists and molecular geneticists, to increase the percentage of genetic diagnosis in cases, to determine the mutation distribution in terms of these diseases in our country, to identify new genes and molecular pathways that cause these diseases with candidate gene approach and functional studies, and we also aimed to provide data for further projects to create a unique IT gene panel that can be used for postnatal diagnosis and screening.</p><p> </p><p> </p><p> In this study whole exome sequencing (WES) wasperformed in 40 patients who have preliminary diagnosis of IT with clinical and primary care examinations. Exome data was investigated for all known and associated IT genes using appropriate. With this approach, in 32 (%80) patients, molecular etiology has been determined. No mutation was detected with WES in 8 patients. The WES data of these case were re-evaluated within the framework of the candidate gene approach and a new candidate gene (ITGA10) that could be responsible for IT was identified. The identified candidate gene was evaluated by functional analysis and the relationship between the genetic defect and the disease was tried to be revealed.</p>