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

Triglyceride Glucose Index and The Triglyceride/HDL Ratio as Predictors of Coronary Artery Disease

Aim: Triglyceride to high density lipoprotein cholesterol (TG/HDL-C) ratio and triglyceride-glucose (TyG) index are simple, reliable screening methods. It has been shown that the TyG index predicts mortality in cardiovascular diseases and the TG/HDL-C ratio predicts the severity of coronary artery disease (CAD). We planned a study to define the relationship between the SYNTAX score, which indicates the severity of CAD, and the TyG index and TG / HDL-C ratio.Material and Methods: A total of 408 patients who underwent coronary angiography were evaluated in this study. TyG index, TG/HDL-C ratio and SYNTAX scores were calculated. Patients were grouped according to their diagnosis and SYNTAX scores. Relationships between TyG index, TG / HDL-C ratio and SYNTAX score were examined.Results: There is a significant relationship between the TyG index and the presence of CAD (p<0.001). When the TyG index was evaluated in terms of the severity of CAD, there was a positive significant relationship between mild and severe CAD (p<0.040). While there was a significant positive correlation between TG/HDL-C ratio and the presence of CAD (p<0.001), there was no significant relationship between severity of CAD (p:0.814). There was a low level significant positive correlation in terms of TyG index between patients with unstable angina pectoris and ST-elevation myocardial infarction (p:0.046).Conclusion: The TyG index and TG/HDL-C ratio are predictors of the presence of CAD and the TyG index also provides guidance on the severity of CAD. Standard use may be considered in addition to risk scoring in the diagnosis of CAD and planning coronary angiography

The importance of speckle tracking echocardiography in the early detection of left ventricular dysfunction in patients with polycystic ovary syndrome

PubMed ID: 26614851Polycystic ovary syndrome (PCOS) is characterized by hormonal and metabolic abnormalities and is thought to increase a risk for cardiovascular diseases. In this study we use speckle tracking echocardiography (STE) to evaluate left ventricular (LV) dysfunction in the early period of the disease. We enrolled 31 patients with PCOS and 32 healthy volunteers as a control group. The participants’ ages ranged between 18 and 40 years. PCOS was diagnosed according to the Rotterdam criteria. LV strain (LS) and strain rate (SR) were evaluated using apical two-chamber (2C), three-chamber (3C), and four-chamber (4C) imaging. Global LS and SR were calculated as average of three apical views. The waist-to-hip ratio, homeostasis model assessment-insulin resistance (HOMA-IR), and fasting insulin and triglyceride levels were higher in the PCOS group than in the controls (p = 0.001, p = 0.001, p = 0.001, and p = 0.005, respectively). In the PCOS group, the mitral A wave, deceleration time (DT), and isovolumetric relaxation time (IVRT) were significantly higher than in the controls (all p < 0.05). The LV global longitudinal strain (GLS) and global longitudinal SR systolic (GLSRS) were significantly lower in the PCOS patient group (both p = 0.001). There were strong negative correlations between GLS and both fasting insulin (r = -0.64) and DT (r =-0.62) (both p < 0.05). The study demonstrated that PCOS patients had decreased LV function using STE. Therefore, STE imaging appears to be useful for the early detection of subclinical LV dysfunction in patients with PCOS. © 2015 ABMSFBIH

Correction to: Primary antibody deficiencies in Turkey: molecular and clinical aspects (Immunologic Research, (2022), 70, 1, (44-55), 10.1007/s12026-021-09242-z)

The original published version of this article contained a mistake in one of the afliations. The correct afliation of author Manolya Kara (7) should read

Mutational landscape of severe combined immunodeficiency patients from Turkey

Severe combined immunodeficiency (SCID) has a diverse genetic aetiology, where a clinical phenotype, caused by single and/or multiple gene variants, can give rise to multiple presentations. The advent of next-generation sequencing (NGS) has recently enabled rapid identification of the molecular aetiology of SCID, which is crucial for prognosis and treatment strategies. We sought to identify the genetic aetiology of various phenotypes of SCIDs and assessed both clinical and immunologic characteristics associated with gene variants. An amplicon-based targeted NGS panel, which contained 18 most common SCID-related genes, was contumely made to screen the patients (n = 38) with typical SCID, atypical SCID or OMENN syndrome. Allelic segregations were confirmed for the detected gene variants within the families. In total, 24 disease-causing variants (17 known and 7 novel) were identified in 23 patients in 9 different SCID genes: RAG1 (n = 5), RAG2 (n = 2), ADA (n = 3), DCLRE1C (n = 2), NHEJ1 (n = 2), CD3E (n = 2), IL2RG (n = 3), JAK3 (n = 4) and IL7R (n = 1). The overall success rate of our custom-made NGS panel was 60% (39.3% for NK+ SCID and 100% for NK- SCID). Incidence of autosomal-recessive inherited genes is more frequently found in our cohort than the previously reported populations probably due to the high consanguineous marriages in Turkey. In conclusion, the custom-made sequencing panel was able to identify and confirm the previously known and novel disease-causing variants with high accuracy.Istanbul Bilgi University; Bilimsel Arastirma Projeleri Birimi, Istanbul Universites