NTNG2 Mutasyonu: Erken nöropsikiyatrik manifestasyonlu yeni bir beyin-cilt hastalığı için aday bir gen mi? 3000 hasta üzerinden bir analiz

Aim: In this study, the relationship between genetic analysis and exome sequencing and clinical and neuroimaging findings of four patients from the same family was investigated by analyzing a clinical and genetic (WES) database containing more than 3000 patients. Methods: We analyzed the WES data of approximately 3000 patients performed in our center in terms of NTNG2 biallelic mutations. In addition, MR imaging findings were investigated. Results: We found four patients with the same mutation in the NTNG2 gene, presenting with similar clinical and neuroimaging findings. As a result of filtering, the c242G>A variant was determined in the NTNG2 gene. In addition, mild to severe brain parenchymal volume loss and frontal and temporal lobe atrophy were seen in cases 1, 2, and 4 on axial T2-weighted MRI. c. Conclusion: The current study has similar phenotypic and genotypic features and is a very rare report showing NTNG2 mutation in this context. Existing clinical data are important in choosing NTNG2 gene-related neuropsychiatric disorders as a future treatment target.Amaç: Bu çalışmada 3000'den fazla hastayı içeren klinik ve genetik (WES) veri tabanını analiz ederek aynı aileden dört hastanın genetik analizi ve ekzom dizilimi ile klinik ve nörogörüntüleme bulguları arasındaki ilişki araştırılmıştır. Yöntem: Merkezimizde 3000 hastanın WES verileri NTNG2 bialelik mutasyonları açısından incelendi. Ayrıca MR görüntüleme bulguları araştırıldı. Bulgular: NTNG2 geninde aynı mutasyona sahip, benzer klinik ve nörogörüntüleme bulguları ile başvuran dört hasta bulundu. Filtreleme sonucunda NTNG2 geninde c.242G>A varyantı belirlendi. Ayrıca aksiyel T2 ağırlıklı MRG'de vaka 1, 2 ve 4'te hafif ila şiddetli beyin parankimal hacim kaybı ve frontal ve temporal lob atrofisi görüldü. Sonuç: Mevcut çalışma benzer fenotipik ve genotipik özelliklere sahip olup bu bağlamda NTNG2 mutasyonunu gösteren çok nadir bir rapordur. Mevcut klinik data NTNG2 geniyle ilişkili nöropsikiyatrik bozukluklarda gelecekteki bir tedavi hedefi olarak seçilmesinde öneme sahiptir

Preoperative screening for COVID-19: Results from a clinical diagnostic laboratory

Objective: The study aimed to determine what proportion of Turkiye’s preoperative patient population has tested positive for COVID-19 and to ascertain whether the increasing or decreasing trend in the numbers of positive preoperative patients resembles the general population of Turkiye during the same period. Materials and Methods: The study cohort involved of the 14,776 patients from various services between January 1-December 31, 2021 who needed preoperative COVID-19 test reports. The patient's SARS-CoV-2 RNA's were detected with real-time polymerase chain reaction (RT-PCR) technique. Results: SARS-CoV-2 RT-PCR positivity was detected in 422 (2.86%) patients, of which 59.72% (n = 252) were female and 40.28% (n = 170) were male; their mean age was 40.2 years. Of the 422 positive cases, 84.12% were young adults (18-65 years), and 9% were middle-aged (66-79 years). Positive cases involving those under the age of 18 were found to account for 5.22% (n = 22) of the total. The highest positivity rate was observed in April 2021 at 8.28% of all test requests, while the lowest positivity rate was observed in June 2021, at 0.36% of all test requests. The highest positivity rate of April was followed by March (5.07%), October (4.74%), and August (3.13%). Conclusion: In conclusion, the COVID-19 RT-PCR positivity rate in the series was detected as 2.85% in preoperative patients over the one year period. Monthly positivity rates in screening results are consistent with the number of cases seen in the general population

The genetic profile of childhood neuromuscular disorders: A single center experience

Neuromuscular Diseases are a heterogeneous group of childhood disorders, and differential diagnosis can be challenging. Although there is no definitive treatment for the most of this group of diseases, early diagnosis is important with the development of new treatment methods. In this study, we aimed to draw attention to the importance of new generation genetic tests in diagnosing neuromuscular diseases. In this retrospective study, we reviewed the records of 800 patients with suspected neuromuscular diseases followed in the Neuromuscular Clinic of Marmara University Pendik Training and Research Hospital between December 2011 and January 2023 according to their demographic, clinical and genetic characteristics. Patients who were diagnosed with Duchenne muscular dystrophy and spinal muscular atrophy with targeted gene testing were excluded from the study. The results of targeted gene testing, clinical exome sequencing (CES), whole exome sequencing (WES) and mitochondrial genome analysis were analysed

Effects of chromosomal translocations on sperm count in azoospermic and oligospermic cases

Purpose: A number of mechanisms have been proposed for the effect of chromosomal translocations on spermatogenesis and sperm maturation. However, there are still numerous ambiguous issues regarding these two processes. The aim of this study is to evaluate the effect of chromosome break areas on sperm count in the light of the literature. Material and Methods: The study was conducted on the data of 16 male patients with reciprocal or Robertsonian translocation among 152 patients who were admitted to Adana Numune Training and Research Hospital and Kanuni Sultan Suleyman Training and Research Hospital Genetic Diagnosis Centers between 2013 and 2016 due to azoospermia and oligospermia. Results: 11 of these patients had reciprocal and five patients had Robertsonian translocations. All the patients with Robertsonian translocations were detected with azoospermia. Of the patients with reciprocal translocation, five of them were azoospermic and six of them were severe oligospermic. Conclusion: A total of 21 chromosomal breakpoints were identified in the 11 patients with reciprocal translocations. These chromosomal breakpoints may contribute to the clarification of ambiguous issues related to spermatogenesis and sperm maturation. The results also showed the importance of genetic counselling in patients with translocations

Detection of α-Thalassemia by Using Multiplex Ligation-Dependent Probe Amplification as an Additional Method for Rare Mutations in Southern Turkey

α-thalassemia is the most common single gene disorder in the Cukurova Region in Turkey. It is therefore routinely screened, including premaritally, in our region. The heterogeneous molecular basis of the disease makes α-thalassemia mutation detection difficult and complex. Besides well established methods, multiplex ligation dependent probe amplification (MLPA) is known as an effective, simple and specific method for the detection and characterization of deletions and duplications. We employed MLPA testing to 30 patients with hematological parameters suggestive of α-thalassemia carrier status but was negative for α-thalassemia with conventional reverse dot blot hybridization (RDB). We found α-globin gene deletions in 3 out of 30 (10 %) patients with MLPA. We propose that MLPA can be used as a second tier test in addition to other techniques such as RDB to identify α-thalassemia carriers in high prevalence regions such as ours, thereby allowing clinicians to provide accurate genetic counselling

Mikobakteriyel hastalıklara mendel duyarlılığı hastalarının genetik ve klinik profili; tek merkez deneyimi

Objective: Mendelian susceptibility to mycobacterial disease (MSMD) is a subgroup of primary immunodeficiencies which develops with the Bacille Calmette–Guérin (BCG) vaccine or non-tuberculous mycobacterial infections. The clinical symptoms have a broad spectrum, from localized to disseminated infections. Materials and Methods: Herein, we performed whole-exome sequencing (WES) on 13 patients with MSMD phenotype. All variants were confirmed by Sanger sequencing. The mean age was 8.41 years (min 3 – max 14 years), and the mean age of symptom onset was 4.6 years in our cohort. Results: We found previously identified IFNGR1 (n=1), IFNGR2 (n=1), TYK2 (n=1), IL12RB1 (n=1), and CYBB (n=1) gene variants in nine patients. Our patients mostly suffered from lymphadenitis (61.5%), osteomyelitis (38%), and miliary tuberculosis (31%). All patients except one had had the BCG vaccination. Two patients developed BCGitis after vaccination. Three patients suffered from disseminated BCG infection (BCGosis). Conclusion: Our findings show the importance of molecular diagnosis in patients with severe infections as an approach for understanding the genetic basis of infectious diseases and deciding on treatment options. The deficiency of IFN-mediated immunity genes plays a crucial role in the pathogenesis of MSMD and must be considered in pediatric patients with BCGitis.Amaç: Mikobakteriyel hastalığa (MSMD) Mendel duyarlılığı, Bacille Calmette-Guérin (BCG) aşısı veya tüberküloz dışı mikobakteriyel enfeksiyonlarla gelişen primer immün yetmezliklerin bir alt grubudur. Klinik semptomlar, lokalize enfeksiyondan yayılmış enfeksiyona kadar geniş bir spektruma sahiptir. Gereç ve Yöntem: Bu çalışmada; MSMD fenotipli 13 hastada tüm ekzom dizileme (WES) yaptık. Tüm varyantlar Sanger dizileme ile doğrulandı. Bizim kohortumuzda ortalama yaş 8.41 yıl (en az 3 – en fazla 14 yıl) ve ortalama semptom başlangıç yaşı 4.6 idi. Bulgular: Dokuz hastada; IFNGR1 (n=2), IFNGR2 (n=1), TYK2 (n=1), IL12RB1 (n=1) ve CYBB (n=1) gen varyantları bulduk. Hastalarımızda en çok lenfadenit (%61,5), osteomiyelit (%38) ve miliyer tüberküloz (%31) mevcuttu. Biri hariç tüm hastalara BCG aşısı yapıldı. İki hastada aşılamadan sonra BCGitis gelişti. Üç hasta, yayılmış BCG enfeksiyonundan (BCGosis) muzdaripti. Sonuç: Bulgularımız, enfeksiyon hastalıklarının genetik temelinin anlaşılmasında ve tedavi seçeneklerine karar verilmesinde bir yaklaşım olarak ağır enfeksiyonlu hastalarda moleküler tanının önemini göstermektedir. IFN aracılı bağışıklık genlerinin eksikliği, MSMD’nin patogenezinde çok önemli bir rol oynar ve BCGitis’li pediatrik hastalarda düşünülmelidir

Clinical, genetic, and outcome characteristics of pediatric patients with primary hemophagocytic lymphohistiocytosis

Objectİive: In this study, we sought to describe the clinical, laboratory, and genetic characteristics of patients diagnosed with primary hemophagocytic lymphohistiocytosis. Thus, we aimed to evaluate the early diagnosis and appropriate treatment options for pediatric hemophagocytic lymphohistiocytosis patients. Materials and Methods: Medical records of 9 patients diagnosed with primary hemophagocytic lymphohistiocytosis between November 2013 and December 2019 were analyzed retrospectively. Clinical, genetic, and laboratory characteristics, family histories, initial complaints, physical examination findings, age at diagnosis, treatment choices, and clinical follow-up of all patients were investigated. Results: The mean age at diagnosis was 11 months (range: 1.5 months to 17 years). Genetic analysis was performed in all patients, and a disease-related mutation was detected in 8 (89%) of them. Among clinical features, 6 (66%) patients had fever, 5 (56%) had splenomegaly, 4 (44%) had lymphadenopathy, 4 (44%) had skin rash, and 4 (44%) had neurological findings. Hemophagocytosis was observed in the bone marrow samples of 6 (66%) patients. Disease remission was achieved in 7 (78%) patients. Hematopoietic stem cell transplantation was performed in 7 (78%) patients. Conclusion: Hemophagocytic lymphohistiocytosis may present with different clinical symptoms that can cause a significant diagnostic delay. The only curative treatment option in primary hemophagocytic lymphohistiocytosis patients is hematopoietic stem cell transplantation. The chemotherapy should be started as early as possible, in order to achieve a disease remission. Patients should be referred to the appropriate bone marrow transplant center for hematopoietic stem cell transplantation as soon as they reach the disease remission

Covid-19: Pathogenesis, genetic polymorphism, clinical features and laboratory findings

COVID-19 caused by a novel agent SARS-CoV-2 progressed to a pandemic condition and resulted in a major public health concern worldwide, leading to social and economic issues at the same time. The pathogenesis of COVID-19 starts with the bonding of the virus to ACE2 receptors expressed in many tissues, and the triggered excessive immune response plays a critical role in the course of the disease. The cytokine storm that occurs upon excessive production of pro-inflammatory cytokines is considered responsible for the severe progression of the disease and the organ damage. However, the accurate pathophysiological mechanism of the disease, which progresses with various clinical presentations, is still substantially unknown. While various studies have been conducted on the effect of genetic polymorphism on the course and severity of the disease, the presence of a significant effect has not been proven yet. The clinical course of the disease is variable, with clinical representation ranging from 81% mild course to 14% severe course along with 5% critical course in patients. Asymptomatic course is considered to be higher than expected, although its frequency is not known exactly. Older adults and those with comorbidities are exposed to a more severe disease course. The disease progress with various symptoms, such as fever, cough, dyspnea, malaise, myalgia, taste and smell dysfunctions, diarrhea, and headache. A range of complications (acute respiratory distress syndrome, thromboembolic conditions, arrhythmia and cardiac events, secondary infections) could be seen during the course of the disease. Varied laboratory tests are vital to determine these verity and prognosis of the disease, along with the condition and exposure of the affected systems during thecourse of COVID-19