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Cystic fibrosis (CF, OMIM: #219700), caused by biallelic pathogenic variations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is the most common monogenic disease. The present study aimed to investigate CFTR gene variations in patients with a positive screening test result for CF and those with a clinical suspicion of CF. Overall, 443 patients (190 females/253 males) were retrospectively included. Of these, a positive neonatal screening test result for CF was reported in 124 patients (58 females/66 males) and a preliminary clinical diagnosis of CF based on recurrent lung infection and/or delayed weight gain was reported in 327 patients (134 females/193 males). All patients were evaluated based on clinical findings, sweat test (ST) results, and CFTR gene sequence analysis results. In the group of 116 patients having a positive neonatal screening test result for CF, heterozygous variations were observed in 21 (18%) patients, compound heterozygous variations in 9 (8%) patients, and homozygous variations in 5 (4%) patients. In the group of 327 patients with a clinical suspicion of CF, heterozygous variations were observed in 52 (16%) patients, compound heterozygous variations in 26 (8%) patients, and homozygous variations in 11 (3%) patients. When the two groups were cumulatively evaluated, the most common mutant alleles were Pro1013Leu (10.4%), Tyr515* (9.6%), and Phe508del (4.8%). In the total study sample of 443 patients, 51 different variants were detected. To the best of our knowledge, this is the first comprehensive study that demonstrated CFTR gene variation distribution in the Eastern Anatolia Region of Turkey. In this study, mutation distribution was highly heterogeneous, and we believe that investigation of the entire CFTR gene is necessary and would improve the diagnostic rates for CF in the Turkish population. [Med-Science 2021; 10(2.000): 293-8]

The aim of this study was to determine the prevalence of leptin (LEP), leptin receptors (LEPR), melanocortin-4-receptor (MC4R), proopiomelanocortin (POMC), single-minded 1 (SIM1), and SH2B1 gene variations in Turkish children and adolescents, and to conduct a detailed examination of the clinical and laboratory findings of patients with variants. In this study, we included 49 children and adolescents (29 male/20 female) who presented to the Pediatric Endocrinology clinic of Erzurum Regional Training and Research Hospital between 2017 and 2020 with obesity. Family history with regards to obesity, parental consanguinity, obesity-related comorbidities, anthropometric measurements, and laboratory tests of the patients were recorded in the clinical evaluation. LEP, LEPR, MC4R, POMC, SIM1, and SH2B1 genes, which are associated with monogenic obesity, were evaluated by the next generation sequencing analysis in all patients. The mean age of 49 patients included in the study was 8.4 ± 5.2 years (range: 0.616.8), their mean height standard deviation score (SDS) was 0.9 ± 1.6, mean body mass index (BMI) was 31.3 ± 8.1 kg/m2, and their mean BMI SDS was 3.5 ± 0.6. A total of four different variants (c.380C>T and c.870delG variants in MC4R gene; c.2992A>C and c.448delA variants in LEPR gene) were detected in four patients. The determination of a molecular etiology in patients with monogenic obesity is important in view of the treatment options to be introduced in the near future (MC4R agonist) and for the family to receive appropriate genetic counseling. In this study, we evaluated the clinical and genetic findings of the patients with monogenic obesity in detail, and contributed the findings of the novel variants to the literature. [Med-Science 2021; 10(2.000): 328-33]

Introduction: Congenital heart defects (CHDs) are the most common congenital anomaly of the newborn with high mortality and morbidity rates. Genetic and environmental risk factors have affect on cardiogenesis. NKX2-5 (NK2 homeobox 5) is a homeobox containing gene which is essential for cardiac differentiation. In this study, our aim was to detect NKX2-5 gene variants associated with CHDs in Turkish population and to better understand genotype- phenotype correlations. Materials and Methods: In this study, we designed primers specific for NKX2-5 gene and sequenced the gene in 80 isolated CHD and 50 control group patients. Patients with chromosomal anomalies, DiGeorge syndrome and multiple congenital anomalies were not included. Results: Most common CHDs seen in the patients were ventricular septal defects (VSD) and atrial septal defects (ASD) (20%), atrioventricular septal defects (AVSD) and tetralogy of Fallot (TOF) (8.75%). We have detected NKX2-5 gene variants in 3.75% of the patients. We found A119S, R161P and C270Y changes in TOF; PFO (patent foramen ovale) with transient supraventricular, ventricular arrhythmia; and ASD patient, respectively. Conclusion: This study is designed to contribute to the genetic variations associated with CHD in Turkish population. NKX2-5 gene R161P variant which is on homeobox domain, was previously reported as pathogenic in an individual with thyroid ectopy and PFO. Further studies are needed to evaluate a possible role of these changes. Genetic testing is important in the follow-up and treatment of patients.

Abstract Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+) are both epilepsy syndromes that can be attributed to deleterious mutations occurring in SCN1A, the gene encoding the pore‐forming α‐subunit of the NaV1.1 voltage‐gated sodium channel predominantly expressed in the central nervous system. In this research endeavor, our goal is to expand our prior cohort of Turkish patients affected by SCN1A‐positive genetic epilepsy disorders. This will be accomplished by incorporating two recently discovered and infrequent index cases who possess a novel biallelic (homozygous) SCN1A missense variant, namely E158G, associated with Dravet syndrome. Furthermore, our intention is to use computational techniques to predict the molecular phenotypes of each distinct SCN1A variant that has been detected to date within our center. The correlation between genotype and phenotype in Dravet syndrome/GEFS+ is intricate and necessitates meticulous clinical investigation as well as advanced scientific exploration. Broadened mechanistic and structural insights into NaV1.1 dysfunction offer significant promise in facilitating the development of targeted and effective therapies, which will ultimately enhance clinical outcomes in the treatment of epilepsy.

Pachydermoperiostosis (PDP), also known as primary hypertrophic osteoarthropathy, is a rare genetic disorder characterized by pachyderma and periostosis. Acromegaly is a condition caused by excessive secretion of growth hormone (GH) leading to elevated insulin-like growth factor 1 levels, and is characterised by somatic overgrowth and physical disfigurement, notably affecting hands and feet. We present two cases referred with an initial diagnosis of acromegaly that were ultimately diagnosed as PDP. Case 1: A 17 year-old boy presented with enlargement in both feet and hands, finger clubbing, swelling in knee joints, knee pain, coarsening of facial skin lines and forehead skin, and excessive sweating which increased gradually over five years. There were prominent skin folds on the forehead, face, and eyelids. Also, there was an enlargement in both hands and clubbing of the fingers. There was marked swelling in the knee joints and ankles. Genetic analysis revealed a novel homozygous variant NM_005630: c.31C>T (p.Q11*) in the SLCO2A1 gene. Case 2: A 16 year-old boy presented with coarsening of forehead skin and scalp, excessive sweating, and pain in the elbow and knee over three years. Skin folds were prominent on the forehead and scalp. Genetic analysis revealed a homozygous variant NM_005630.2: c.86delG (p.G29Afs*48) in the SLCO2A1 gene. Such clinical presentation contemporaneous with normal GH level and prominent radiological abnormalities prompted the diagnosis of PDP. In conclusion, PDP is a very rare osteoarthrodermopathic disorder with clinical and radiographic presentation that may mimic acromegaly. In the evaluation of patients with acromegaloid appearance, PDP should be considered as a differential diagnosis.