Gokhan Ozan Cetin

This study aimed to determine the incidence of chronic thromboembolic pulmonary hypertension (CTEPH) following acute pulmonary embolism (PE) and to identify associated risk factors. A total of 256 adult patients diagnosed with acute PE in 2018 and 2019 at a tertiary care center were retrospectively evaluated. Diagnostic and follow-up procedures included clinical scoring, echocardiography, computed tomography pulmonary angiography (CTPA), and/or ventilation/perfusion (V/Q) scintigraphy. To assess the development of CTEPH, we analyzed baseline characteristics and follow-up data for each cohort over a two-year period: 2018 to 2020 for patients diagnosed in 2018, and 2019 to 2021 for those diagnosed in 2019. Right heart catheterization (RHC) findings and follow-up imaging at the third and sixth months were reviewed. Demographic, clinical, laboratory, and radiological variables were compared between patients with and without CTEPH. The incidence of CTEPH was 7.8% (n=20). Right ventricular (RV) dilatation at initial imaging was significantly more frequent in the CTEPH group (p=0.042). At both the third and sixth months, elevated systolic pulmonary artery pressure (sPAP) >50 mmHg, tricuspid regurgitation (TR), and tricuspid regurgitation velocity (TRV) >2.8 m/s were significantly more common in CTEPH patients (p<0.05). No significant association was found with genetic thrombophilia, whereas antiphospholipid antibodies and lupus anticoagulant were more prevalent but not statistically significant. Although rare, CTEPH is associated with high morbidity and mortality but remains potentially curable if diagnosed early. Early signs such as RV dysfunction may help identify high-risk patients. Therefore, structured follow-up protocols are essential to ensure timely diagnosis and referral to specialized centers.

Objectives: Osteoporosis (OP) is a usual disease with a possible genetic predisposition. IL-23 plays a role in physiological bone remodeling and regulates the activity of cells of the bone either directly or indirectly on bone-resorbing osteoclasts as well as on bone-forming osteoblasts. Recent animal and human trials have revealed the main pro-osteoclastogenic activities for the IL-23 pathway. We examined nine single nucleotide polymorphisms (SNPs) in the interleukin-23 receptor (IL-23R) in 100 OP patients and gender- and age-matched 96 healthy volunteers. The most analyzed SNPs in the recent rheumatology literature were selected. Methods: In addition to gene polymorphisms several laboratory parameters (osteocalcin, parathormone, vitamine D) were investigated. Independent Samples t-test and Mann-Whitney-U test were used to compare several demographic and clinical parameters between the groups. P-value < 0.05 was accepted to be statistically significant. Results: Having the heterozygous GA genotype of IL-23R rs1004819 and the heterozygous CT genotype of Il-23R rs7530511 significantly increase the risk of developing OP (adjusted OR: 3.51, p = 0.031 and OR: 2.41, p = 0.027, respectively). The wild homozygous GG genotype of Il-23R rs11209032 had higher osteocalcin levels compared with the mutant homozygous AA genotype (18.75 ± 9.76, p = 0.009). Conclusions: Our findings suggest that several IL-23R gene polymorphisms are seen more often in osteoporosis patients than in healthy volunteers. In addition, some SNPs were related to higher serum osteocalcin levels.

Purpose: The aim of study was to determine the relation of vitamin D receptor gene (VDR) polymorphisms of TaqI (rs731236), ApaI (rs7975232), BsmI (rs1544410), FokI (rs10735810) with the risk of obesity, metabolic syndrome and hepatosteatosis in children. Materials and methods: 130 obese and 130 healthy children of age range between 10-16 years included in this study. Anthropometric measurements, biochemical evaluations and abdominal USG of all children were done. Obese and healty children were analyzed for the most common polymorphisms of the VDR gene by restriction fragment length polymorphism’s technique. The diagnosis of metabolic syndrome was made using the International Diabetes Federation criteria. Results: Genotypic distribution of BsmI, FokI, and TaqI polymorphism were found statistically different between obese patients and control group, but genotypic distribution of all studied polymorphisms were not found statistically different in obese patients with metabolic syndrome or hepatosteotosis. Conclusion: BsmI polymorphism (rs1544410) was found to have a significant positive effect on the development of obesity, metabolic syndrome and hepatosteatosis. Children who carry risk factors for childhood obesity could be screened before the development of obesity and associated metabolic complications using the BsmI polymorphism of the VDR gene.

Koolen‐de Vries syndrome (KdVS) is a rare multisystemic disorder caused by a microdeletion on chromosome 17q21.31 including KANSL1 gene or intragenic pathogenic variants in KANSL1 gene. Here, we describe the clinical and genetic spectrum of eight Turkish children with KdVS due to a de novo 17q21.31 deletion, and report on several rare/new conditions. Eight patients from unrelated families aged between 17 months and 19 years enrolled in this study. All patients evaluated by a clinical geneticist, and the clinical diagnosis were confirmed by molecular karyotyping. KdVS patients had some common distinctive facial features. All patients had neuromotor retardation, and speech and language delay. Epilepsy, structural brain anomalies, ocular, ectodermal, and musculoskeletal findings, and friendly personality were remarkable in more than half of the patients. Hypertension, hypothyroidism, celiac disease, and postaxial polydactyly were among the rare/new conditions. Our study contributes to the clinical spectrum of patients with KdVS, while also provide a review by comparing them with previous cohort studies.

Hereditary spastic paraplegias (HSP) are a group of inherited, neurodegenerative disorders characterized by progressive gait impairment, lower extremity spasticity and increased patellar reflexes. More than 80 types of HSP have been defined to date. In complicated forms, lower limb spasticity and gait impairment is accompanied by an additional neurological finding. Autosomal recessive (AR) HSPs are usually identified in complicated forms and occur more frequently in countries where consanguineous marriage is more widespread. Next generation sequencing techniques, developed in the last decade, have led to the identification of many new types of HSP and reduced the “diagnostic odyssey.” Whole exome sequencing (WES) can diagnose up to 75% of undiagnosed HSP patients. Targeted genetic analysis with good clinical phenotyping gives the best diagnostic yields for rare diseases. Clinical heterogeneity is prominent in AR complicated HSP. However, some clinical features complicating the disease or magnetic resonance imaging findings, including thin corpus callosum or white matter abnormalities, can help to distinguish some types. AR spastic paraplegia type 64 (SPG64) is a very rare HSP, caused by a mutation in the ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) gene, first described in 2014. To date only nine patients from five families have been reported. We present two siblings with a novel pathogenic variant in ENTPD1, diagnosed by WES, as the sixth published family. We propose that early onset in childhood, cognitive impairment, dysarthria/anarthria, dystonia and areflexia may be the distinctive features of SPG64 and more clinical evidence from families with pathogenic ENTPD1 variants is warranted.

X-linked retinoschisis is an inherited retinal disease caused by mutations in the RS1 gene; however, a genotype-phenotype correlation regarding the mutation type or location within the RS1 gene and...

OBJECTIVE: We aimed to determine the hot spot mutational frequencies of Enhancer of Zeste homolog 2 (EZH2) and cluster of differentiation 79B (CD79B) genes in a cohort of mature B-cell non-Hodgkin's lymphomas. PATIENTS AND METHODS: DNA samples from formalin-fixed and paraffin embedded (FF-PE) tissues from a total of 37 patients with mature B-cell non-Hodgkin lymphomas were included in the study. Molecular genetic analysis was performed by direct sequencing of the DNA samples. RESULTS: We analyzed formaldehyde fixed-paraffin embedded (FFPE) tumor tissue samples from 17 female and 20 male patients with a median age of 63.7 years at the time of diagnosis. None of the patients had previously reported hot spot mutations in EZH2 and CD79B, but previously unreported single nucleotide variations of CD79B were present in nine patients. rs779833118 was the most frequent variation (7/37 patients, 18.9%). A non-synonymous variation rs757407417, which could have a potentially damaging outcome, was detected in two patients. CONCLUSIONS: None of the patients had well-known hot spot mutations in EZH2 and CD79B. However, we detected novel CD79B variations in mature B-cell non-Hodgkin's lymphoma patients.

The Wnt planar cell polarity (PCP) pathway is one of the Wnt pathways which plays a critical role in cell proliferation and fate. The VANGL1 protein is one of Wnt-PCP pathway components. It is known that Wnt-PCP pathway has major roles in cell motility but its role in hepatocellular carcinoma (HCC) progression through invasion and metastasis needs to be clarified. We silenced VANGL1 gene expression in the HepG2 HCC cell line by stable transfection with a vector containing siRNA template for VANGL1 and investigated the change in cell invasion and motility. Transfected cells with the siRNA template showed significantly suppressed invasive capacity when compared to controls although cellular motility was only slightly affected. Our study showed a basal role for VANGL1 with respect to the invasive capacity of HCC cells. This suggests that the Wnt-PCP pathway may play a role in progression of HCC through cellular invasion but further studies are needed to clarify its role in cell motility.

BackgroundTo investigate the association between age-related macular degeneration (AMD) and the polymorphisms of HIF1A, a major vascular epithelial growth factor regulator under hypoxic conditions. The associations of AMD and polymorphisms of genes CFH, SKIV2L and MYRIP were also studied. DesignProspective study. ParticipantsEighty-seven AMD patients and 80 healthy subjects admitted to the Department of Ophthalmology at Pamukkale University Hospital, Denizli, Turkey, were included: 45 (52%) had wet type AMD, and 42 (48%) had dry type AMD. MethodsPolymorphisms rs1061170 (CFH), rs429608 (SKIV2L), rs2679798 (MYRIP) and both rs11549465 and rs11549467 (HIF1A) were investigated in DNA isolated from peripheral blood samples of the cases and controls by dye-termination DNA sequencing. Main Outcome MeasuresGenotype distribution of rs1061170 (CFH), rs429608 (SKIV2L), rs2679798 (MYRIP) and both rs11549465 and rs11549467 (HIF1A) in AMD cases and healthy controls; association between genotypes and AMD subtypes. ResultsGiven the significant difference between the mean age of case and control groups (72.135.77 vs. 62.80 +/- 5.22, respectively) (P=.000), subsequent analyses were adjusted for age. We found that having at least one C allele for polymorphism rs1061170 increases AMD risk independent of age (OR=2.42, 95% confidence interval [CI], 1.22-4.81). The ancestral T allele for polymorphism rs1061170 has a protective effect for AMD (OR=0.53, 95% CI, 0.34-0.83). No statistically significant difference for distributions of other single nucleotide polymorphisms (SNPs) emerged between patients and healthy subjects. ConclusionsNo associations appeared between HIF1A SNPs and AMD, which were studied here for the first time; however, polymorphism rs1061170 of the CFH gene is associated with AMD in our population.