The Role of Polymorphisms in Graves' Disease with or without Ophthalmopathy in a Turkish Population.

Objectives: Forkhead box P3 () gene polymorphisms have been evaluated in many autoimmune diseases, including Graves' disease (GD), in different populations. However, those polymorphisms have not been analyzed in GD or Graves' ophthalmopathy (GO) in the Turkish population. In this study, we aimed to evaluate the frequency of polymorphisms in GD with or without ophthalmopathy in a Turkish population.

Novel Indole-Pyrazole Hybrids as Potential Tubulin-Targeting Agents; Synthesis, antiproliferative evaluation, and molecular modeling studies.

Structurally diverse indole-3-pyrazole-5-carboxamide analogues () were designed, synthesized, and evaluated for their antiproliferative activity against three cancer cell lines (Huh7, MCF-7, and HCT116) using the sulforhodamine B assay. Some of the derivatives showed anticancer activities equal to or better than sorafenib against cancer cell lines. Compounds showed potent activity against the hepatocellular cancer (HCC) cell lines, with IC values in the range 0.

Vicinal Diaryl-Substituted Isoxazole and Pyrazole Derivatives with Growth Inhibitory and Antitumor Activity.

The vicinal diaryl heterocyclic framework has been widely used for the development of compounds with significant bioactivities. In this study, a series of diaryl heterocycles were designed and synthesized based on an in-house diaryl isoxazole derivative (), and most of the newly synthesized derivatives demonstrated moderate to good antiproliferative activities against a panel of hepatocellular carcinoma and breast cancer cells, exemplified with the diaryl isoxazole and the diaryl pyrazole with IC values in the range of 0.7-9.

The effect of apoprotein E gene polymorphism on neurocognitive functions of children with CHD.

Studies have demonstrated an association between CHD and neurodevelopmental delay. This delay is associated with many factors like reduced blood flow and oxygen, cardiac catheterisations, and genetic factors. Apo E gene polymorphism is one of these genetic factors.

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.

Identification of an mRNA isoform switch for HNRNPA1 in breast cancers.

Roles of HNRNPA1 are beginning to emerge in cancers; however, mechanisms causing deregulation of HNRNPA1 function remain elusive. Here, we describe an isoform switch between the 3'-UTR isoforms of HNRNPA1 in breast cancers. We show that the dominantly expressed isoform in mammary tissue has a short half-life.

Synthesis of novel indole-isoxazole hybrids and evaluation of their cytotoxic activities on hepatocellular carcinoma cell lines.

Background: Liver cancer is predicted to be the sixth most diagnosed cancer globally and fourth leading cause of cancer deaths. In this study, a series of indole-3-isoxazole-5-carboxamide derivatives were designed, synthesized, and evaluated for their anticancer activities. The chemical structures of these of final compounds and intermediates were characterized by using IR, HRMS, H-NMR and C-NMR spectroscopy and element analysis.

EGF-SNX3-EGFR axis drives tumor progression and metastasis in triple-negative breast cancers.

Epidermal growth factor receptor (EGFR) has critical roles in epithelial cell physiology. Over-expression and over-activation of EGFR have been implicated in diverse cancers, including triple-negative breast cancers (TNBCs), prompting anti-EGFR therapies. Therefore, developing potent therapies and addressing the inevitable drug resistance mechanisms necessitates deciphering of EGFR related networks.

Genome-wide association and whole exome sequencing studies reveal a novel candidate locus for restless legs syndrome.

Introduction: The restless legs syndrome (RLS) is a common heritable neurologic disorder which is characterized by an irresistible desire to move and unpleasant sensations in the legs.

Methods: We aim to identify new variants associated with RLS by performing genome-wide linkage and subsequent association analysis of forty member's family with history of RLS.

Results: We found evidence of linkage for three loci 7q21.

Is cervical swab an efficient method for developing a new noninvasive prenatal diagnostic test for numerical and structural chromosome anomalies?

Background/aim: Prenatal diagnosis is vital to obtain healthy generation for risky pregnancies. There have been several approaches, some of which are routinely applied in clinics to evaluate the possible prenatal deficiencies and/or diseases. In the present study, we aimed to isolate the fetal cells from endocervical samples and try to identify possible anomalies which were proved by Amniocentesis (AS) and chorionic villus sampling (CVS) methods.

Inherited eye diseases in Turkey: Current approaches and future directions.

The aim of this review is to reveal Turkey's current status of medical practice in inherited eye diseases and the necessary steps to improve healthcare services and research activities in this area. Since consanguinity rate is high, disease burden is estimated to be high in Turkey. Universal health insurance system, easily accessible medical specialists, increasing genetic test, and counseling opportunities are the key advantages of Turkey's healthcare system.

Intelligent Ratio: A New Method for Carrier and Newborn Screening in Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is an inherited, autosomal recessive neuromuscular disease that causes high morbidity and mortality. The prevalence is 1-2/100,000, while the incidence is 1/6000-1/10,000 among live births. Due to the high carrier frequency (1/40-1/60) of SMA-associated alleles, screening can prevent new cases.

Aetiological Evaluation of Oligodontia in a Three-Generation Family.

Purpose: The aim of this study was to assess the genetic evaluation of a three-generation consanguineous family with isolated oligodontia.

Materials And Methods: A 16-year-old male patient who had been referred for orthodontic treatment due to the presence of oligodontia, and his family members who presented several missing teeth had been enrolled in the study. Clinical and radiological assessments and genetic analysis including whole-exome sequencing were performed.

Identification of small-molecule urea derivatives as novel NAMPT inhibitors via pharmacophore-based virtual screening.

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the condensation of nicotinamide (NAM) with 5-phosphoribosyl-1-prophosphate (PRPP) to yield nicotinamide mononucleotide (NMN), a rate limiting enzyme in a mammalian salvage pathway of nicotinamide adenine dinucleotide (NAD) synthesis. Recently, intracellular NAD has received substantial attention due to the recent discovery that several enzymes including poly(ADP-ribose) polymerases (PARPs), mono(ADP-ribose) transferases (ARTs), and sirtuins (SIRTs), use NAD as a substrate, suggesting that intracellular NAD level may regulate cytokine production, metabolism, and aging through these enzymes. NAMPT is found to be upregulated in various types of cancer, and given its importance in the NAD salvage pathway, NAMPT is considered as an attractive target for the development of new cancer therapies.

Pharmacophore modeling and virtual screening studies to identify novel selective SIRT2 inhibitors.

Sirtuins (SIRTs) are a class of NAD-dependent protein histone deacetylases (HDACs) that catalyse the reversible deacetylation of lysine residues in the histones or non-histone substrates. Mammalian sirtuins consist of seven isoforms (SIRT1-7), which show different subcellular localizations and enzymatic functions. Among the seven human sirtuins, SIRT2 predominantly located in the cytoplasm but is enriched in the nucleus during mitosis.

Identification of Three Novel FBN1 Mutations and Their Phenotypic Relationship of Marfan Syndrome.

Background: Marfan syndrome (MS), a connective tissue disorder that affects ocular, skeletal, and cardiovascular systems, is caused by heterozygous pathogenic variants in FBN1. To date, over 1800 different pathogenic variants have been reported.

Methods: In the present study, FBN1 sequence analysis was performed in a family and two unrelated patients with MS.

Single-Nucleotide Polymorphisms in IL23R-IL12RB2 (rs1495965) Are Highly Prevalent in Patients with Behcet's Uveitis and Vary Between Populations.

: To test the frequency of single-nucleotide polymorphisms in the genes in patients with Behcet's uveitis. : Blood samples were collected from 89 Israeli and Turkish patients, and from healthy control subjects of different origins. Genomic DNA was extracted from peripheral blood leukocytes and genotyped.

LRP5-linked osteoporosis-pseudoglioma syndrome mimicking isolated microphthalmia.

Microphthalmia is defined as the measurement of the total axial length of the eyeball to be below average of the two standard deviation according to the age. While several genes have been identified so far related to microphthalmia, the genetic etiology of the disease has not been fully understood because of genetic heterogeneity observed in this disease. After exclusion of the genes that had been known to be the cause of microphthalmia, we performed homozygosity mapping and exome sequencing to clarify the genetic etiology of the bilateral microphthalmia in this family.

Genetic analysis of and in Turkish patients with corneal dystrophies: Five novel variations in .

Purpose: To identify pathogenic variations in () and () genes in Turkish patients with corneal dystrophy (CD).

Methods: In this study, patients with macular corneal dystrophy (MCD; n = 18), granular corneal dystrophy type 1 (GCD1; n = 12), and lattice corneal dystrophy type 1 (LCD1; n = 4), as well as 50 healthy controls, were subjected to clinical and genetic examinations. The level of antigenic keratan sulfate (AgKS) in the serum samples of patients with MCD was determined with enzyme-linked immunosorbent assay (ELISA) to immunophenotypically subtype the patients as MCD type I and MCD type II.

Influence of Folate-Related Gene Polymorphisms on High-Dose Methotrexate-Related Toxicity and Prognosis in Turkish Children with Acute Lymphoblastic Leukemia.

Objective: High-dose methotrexate (HD-MTX) is widely used in the consolidation phase of childhood acute lymphoblastic leukemia (ALL), but the roles that polymorphisms in folate-related genes (FRGs) play in HD-MTX toxicity and prognosis in children with ALL are not understood. The aims of this study were to investigate the frequencies of polymorphisms in the genes for thymidylate synthase (TS), methionine synthase reductase (MTRR), and methylene tetrahydrofolate reductase (MTHFR) in Turkish children with ALL and to assess associations between these polymorphisms and HD-MTX-related toxicity and leukemia prognosis in this patient group.

Materials And Methods: FRG polymorphisms were assessed by real-time polymerase chain reaction.

Evaluation of GenoFlow Thrombophilia Array Test Kit in its detection of mutations in Factor V Leiden (G1691A), prothrombin G20210A, MTHFR C677T and A1298C in blood samples from 113 Turkish female patients.

Thrombophilia is a heritable blood disease characterized by an increased tendency to form abnormal blood clots that can block blood vessels. In obstetrics and gynecology, it has been shown by a number of reports that a proportion of recurrent miscarriages involve thrombophilia-related mutations, in particular, Factor V G1691A, prothrombin G20210A, and MTHFR C677T and A1298C. In this study, we examined the frequency of these four mutations in 113 female Turkish patients who had prior complications in pregnancy, using the DiagCor GenoFlow Thrombophilia Array Test kit.