Barış PAKSOY

Background: Alpha-thalassemia is one of the most common hereditary hemoglobin disorders worldwide and is caused mainly by deletions in the α-globin gene cluster. Understanding the regional mutation spectrum is important for screening programs and genetic counseling. Methods: This retrospective study included 115 patients evaluated for suspected alpha-thalassemia in Antalya, Türkiye. Molecular analysis was performed using multiplex ligation-dependent probe amplification (MLPA) to detect deletions and duplications in the α-globin gene cluster. Hematological parameters and hemoglobin (Hb) fractions were analyzed and compared among mutation groups. Results: The most frequent mutation detected was the −α^3.7 deletion followed by the (−α)^20.5 deletion. Patients with compound heterozygous deletions demonstrated lower Hb, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) values compared with other groups. Significant correlations were observed between Hb levels and red blood cell (RBC), MCV, and MCH, while red cell distribution width (RDW) showed an inverse relationship. Conclusions: The results demonstrate that −α^3.7 and (−α)^20.5 are the predominant α-globin gene variants in the Antalya region. These findings contribute to the characterization of the α-thalassemia mutation spectrum in a clinical cohort and may help improve carrier screening strategies, prenatal diagnosis programs, and genetic counseling services.

Objective: The aim of this study is to determine whether there is a genetic predisposition in young patients with transitional cell carcinoma (TCC) of the bladder. Material And Methods: Data were collected from a total of 652 patients who underwent transurethral resection of bladder tumor (TUR-BT) between January 2010 and January 2021. Seven patients under the age of 40, non-smokers, and without occupational predisposing factors to urinary tract TCC were included in the study. Age, body mass index (BMI), sex, occupation, and five-year follow-up were collected retrospectively. A total of 403 cancer-related genes were analyzed from the patients’ blood samples. The Clinical Exome Sequencing test was used to identify genetic mutations. Results: Six of the patients were male and one patient was female. The mean age and BMI were 31.42 ± 2.12 (22-39) years and 21.72 ± 33.14 (22-27.7) kg/m2, respectively. None of the patients had a first-degree relative with urinary tract TCC. Of all the patients, only one patient had a deletion of exons 1 to 17 in the breakpoint cluster region gene. Conclusion: Genetic predisposing factors in young bladder TCC have not been clearly identified. Although our study included a limited number of patients, our results showed no genetic predisposition in young patients with bladder TCC without family history of bladder cancer. To evaluate the exact relationship, prospective randomised controlled trials with larger numbers of patients are needed.

AMAÇ: JAK2V617F mutasyonu pozitifliği kronik miyeloproliferatif neoplazilerin (KMPN) tanısı için ana kriterdir. Mutasyon yükünün belirlenmesi çoğu moleküler laboratuvarda standart bir tanı prosedürü haline gelmiştir, ancak KMPN tanısı için bir sınır değer belirtilmemektedir. Burada, JAK2V617F mutasyon yükü düşük ve yüksek olan miyeloproliferatif neoplazi ön tanılı hastaların klinik ve hematolojik parametreler açısından karşılaştırılması amaçlandı. GEREÇ VE YÖNTEM: Sağlık Bilimleri Üniversitesi Antalya Eğitim ve Araştırma Hastanesi tıbbi genetik kliniğinde 2019 - 2021 yılları arasında JAK2V617F mutasyonu pozitif olan 95 hasta retrospektif olarak analiz edildi. BULGULAR: Allel yükü düşük (≤%3) olan 46 hastanın %64'ü KMPN fenotipine sahipken, yüksek allel yükü (>%3) olan 49 hastanın %100'ü KMPN fenotipine sahipti. Her iki grup arasında eritrosit sayısı, hemoglobin düzeyi, ortalama eritrosit hacimleri arasında istatistiksel bir fark bulunmazken; lökosit, nötrofil ve trombosit yüksekliği JAK2V617F allel yükü >%3 olan grup lehine istatistiksel olarak anlamlı bulundu (p=0.007; p<0.001; p%3 olan tüm hastalara KMPN tanısı konulmuştur; bu nedenle, bu sınırın üzerindeki bir mutasyon yükü, miyeloproliferatif bir hastalığın varlığın göstergesi olarak kabul edilebilir. Düşük allel yüklü JAK2V617F mutasyonuna yaklaşımı tanımlamak için standardize edilmiş moleküler yöntemlerle prospektif olarak incelenen daha büyük hasta gruplarına sahip çalışmalara ihtiyaç vardır.

Retinitis pigmentosa is an inherited degenerative disorder causing severe retinal dystrophy and visual impairment, mainly with onset in the first or second decades. The next-generation sequencing has become an efficient tool to identify disease-causing mutations in retinitis pigmentosa. The aim of this retrospective study was to investigate novel gene variants and evaluate the utility of whole-exome sequencing in patients with retinitis pigmentosa.

Objective: The current study aimed to retrospectively evaluate different diag- nostic approaches for the array genetic analysis of the cases from all trimester fetal loss in the medical genetics clinic between 2016 and 2017. The Quantitati- ve Fluorescent Polymerase Chain Reaction(QFPCR) test was performed on 50 samples, and aneuploidy was detected in 11 samples as a result of the test, and the array-CGH was performed when 39 QF-PCR resulted in normal test results. Under this purpose, we aimed to analyze and determine the possible copy num- ber variation(CNV), gene deletions, and/or duplications involved in embryonic cell division, tissue differentiation, intended.Materials and methods: DNA isolation from cases of this retrospective study was completed using the PureLink Genomic DNA isolation kit. DNA samples were then genoty - ped for molecular etiological reasons by oligonücleotid microarray -CGH method (aCGH , 60 K ISCA design , Agilent , Germany ). Hybridized probe correlations of the case and reference DNAs were evaluated with databases (Database of Genomic Variants Analysis ) used in genomic variation analysis in terms of 54 functional genes CNVs associated with intrauterine losses.Results: CNV was detected in 30 (77%) of 39 fetal samples analyzed within the scope of the research. Fifty-five percent of CNVs were found to be duplication (55%) and forty-five percent were deletions (45%). As a result of the evaluation, deletion was detected in 19 (35%) of 54 genes, duplication was detected in 26 (48%), while in 3 (6%) both deletion and duplication were detected. Although CNV detected in autosomal chromosomes (chromosome 1, 2, 3, 4, 5, 7, 8, 10, 12, 13, 14, 15 and 20), CNV was established the most common in X chromosome. In our study, CNVs associated with COX7B, ZIC1, MECP2, FMR1, HOXD13, JAG1, MSX2, NEXN, and SIX3 genes were found to be more frequent in terms of fetal loss etiology.Conclusions: Based on our experience, the array-CGH method can be used to investigate the etiology of the normal results of QF-PCR in cases of fetal loss. The array CGH method will be preferred more and more due to the ease of application and the data obtained. When we look at the literature, it is seen that there is not enough research on array CGH about fetal loss and more studies are needed to increase the experience in this field.