Impact of Fluorescent In Situ Hybridization Aberrations and CLLU1 Expression on the Prognosis of Chronic Lymphocytic Leukemia: Presentation of 156 Patients from Turkey

Objective: This study evaluates the impact of CLLU1 expression and fluorescent in situ hybridization (FISH) analysis of a group of Turkish chronic lymphocytic leukemia (CLL) patients. Materials and Methods: A total of 156 CLL patients were analyzed by FISH method; 47 of them were also evaluated for CLLU1 expression. Results were correlated with clinical parameters. Results: FISH aberrations were found in 62% of patients. These aberrations were del13q14 (67%), trisomy 12 (27%), del11q22 (19%), del17p (8%), and 14q32 rearrangements (20%). Overall del11q22 and del17p were associated with the highest mortality rates, shortest overall survival (OS), and highest need for medication. Homozygous del13q14, 14q32 rearrangements, and higher CLLU1 expression correlated with shorter OS. Conclusion: Cytogenetics/FISH analysis is still indicated for routine evaluation of CLL. Special consideration is needed for the poor prognostic implications of del11q22, del17p, 14q32 rearrangements, and homozygous del13q14. The impact of CLLU1 expression is not yet clear and it requires more data before becoming routine in genetic testing in CLL patients

Identification of three novel pathogenic ITGA2B and one novel pathogenic ITGB3 mutations in patients with hereditary Glanzmann’s thrombasthenia living in Eastern Turkey

Glanzmann’s thrombasthenia (GT) is an autosomal recessive disorder in which the underlying problem is the lack or dysfunction of the GpIIb/IIIa receptor on the platelet surface. The present study determines the genetic mutation typology and analyzes the association between mutation types and clinical findings in patients diagnosed with GT who were followed up in Department of Pediatric Hematology of the Yüzüncü Yıl University School of Medicine. The medical charts of 17 patients who underwent therapy and that were followed up in the Department of Pediatric Hematology of the Yüzüncü Yıl University Dursun Odabaş Medical Center between January 2008 and April 2018 were reviewed retrospectively. Data on such patient characteristics as present genetic mutations, age, gender, age at diagnosis, presenting symptoms, clinical findings, and platelet count and volume were garnered from the patient records. Of the 12 patients identified with genetic mutations, six had the same type of mutation, while four were identified with novel mutations that have to date not been defined in literature. Of these four mutations, three were located in the ITGA2B gene and one in the ITGB3 gene. The present study identified no significant association between the genetic and clinical findings of the patients. Novel mutations were identified in four cases in the present study. No association was found between the mutation type, and the bleeding scores and bleeding phenotypes of the patients. Further studies involving a larger number of patients are required to determine the relationship between the genotypes and clinical findings in patients with GT

Clinical and molecular evaluation of MEFV gene variants in the Turkish population: a study by the National Genetics Consortium

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease