Can prothrombotic gene variants and Apoa1 rs5069 polymorphism be the predictors of early myocardial infarctions?

Background/aim: We aimed to determine the genetic risk factors in patients aged 45 years and below with a history of early myocardial infarction (MI), compared to individuals over 60 years of age with no history of MI. Materials and methods: In this study, we selected different age groups to more clearly distinguish genetic differences. Accordingly, we compared individuals who had experienced MI at an early age with those who were older and had not experienced any cardiovascular events. The patient group consisted of 99 volunteers under the age of 45 with a history of MI, while the control group included 99 volunteers aged 60 and over without a history of MI. MTHFR (C677T, A1298C), Factor V Leiden (G1691A), Prothrombin (G20210A), PAI (4G/5G), Factor XIII (V34L), APOA1 (rs670, rs1799837, rs5069), and APOB were studied using blood samples taken from the patients. Results: In the logistic regression analysis of thrombophilia markers and gene polymorphisms in the patient and control groups, no statistically significant increase was observed in markers other than APOA1 rs5069 gene polymorphism. APOA1 rs5069 gene polymorphism was found to be higher in the patient group than those without this polymorphism. The frequencies of homozygous MTHFR (C677T, A1298C) and heterozygous Factor XIII V34L were higher in the patient cohort compared to the controls. Conclusion: In our study, we found that prothrombotic gene variants and APOA1 rs5069 polymorphism were statistically significantly associated with coronary artery disease. Thus, prothrombotic gene variants and APOA1 rs5069 polymorphism may serve as predictors of early myocardial infarctions. Individuals with early family histories of coronary artery disease could be screened for these mutations.

NDE1-related disorders: A recurrent NDE1 pathogenic variant causing Lissencephaly 4 can also be associated with microhydranencephaly.

NudE Neurodevelopment Protein 1 (NDE1) gene encodes a protein required for microtubule organization, mitosis, and neuronal migration. Biallelic pathogenic variants of NDE1 gene are associated with structural central nervous system abnormalities, specifically microlissencephaly and microhydranencephaly. The root of these different phenotypes remains unclear. Here, we report a 20-year-old male patient referred to our clinics due to severe microcephaly, developmental delay, spastic quadriplegia, and dysmorphic features. The cranial computed tomography revealed abnormal brain structure and excess of cerebrospinal fluid, consistent with microhydranencephaly. A homozygous c.684_685del, p.(Pro229TrpfsTer85) change in NDE1 gene was found by clinical exome analysis. The variant has previously been reported in individuals with microlissencephaly, therefore we propose that the same variant within the gene may cause either microlissencephaly or microhydranencephaly phenotypes. There are only a few papers about NDE1-related disorders in the literature and the patient we described is important to clarify the phenotypic spectrum of the disease.

An Anomaly with Potential as a New Prognostic Marker in CLL with del(13q): Gain of 16p13.3.

Deletion 13q [del(13q)] is a favorable prognostic marker if it is detected as a sole abnormality in chronic lymphocytic leukemia (CLL). However the clinical courses of cases with isolated del(13q) are quite heterogeneous. In our study, we investigated copy number variations (CNVs), loss of heterozygosity (LOH), and the size of del(13q) in 30 CLL patients with isolated del(13q). We used CGH+SNP microarrays in order to understand the cause of this clinical heterogeneity. We detected del(13q) in 28/30 CLL cases. The size of the deletion varied from 0.34 to 28.81 Mb, and there was no clinical effect of the deletion size. We found new prognostic markers, especially the gain of 16p13.3. These markers have statistically significant associations with short time to first treatment and advanced disease stage. Detecting both CNVs and LOH at the same time is an advantageous feature of aCGH+SNP. However, it is very challenging for the array analysis to detect mosaic anomalies. Therefore, it is very important to confirm the results by FISH. In our study, we detected approximately 9% mosaic del(13q) by microarray. In addition, the gain of 16p13.3 may affect the disease prognosis in CLL. However, additional studies with more patients are needed to confirm these results.

A Turkish patient with novel AHCY variants and presumed diagnosis of S-adenosylhomocysteine hydrolase deficiency.

S-adenosylhomocysteine hydrolase deficiency is an autosomal recessive neurometabolic disorder affecting the muscles, liver, and nervous system. The disease occurs by pathogenic variants of AHCY gene encoding S-adenosylhomocysteine hydrolase (AHCY) enzyme. This article reports a patient with presumed AHCY deficiency who was diagnosed by whole exome sequencing due to compound heterozygosity of novel p.T57I (c.170C>T) and p.V217M (c.649G>A) variants of AHCY gene. The patient had diffuse edema, coagulopathy, central nervous system abnormalities, and hypotonia. She died in 3 months due to cardiovascular collapse. Clinical findings of the present case were compatible with previously reported AHCY deficiency patients and the novel variants we found are considered to be the cause of the symptoms. This article also compiles the previous reports and expands clinical spectrum of AHCY deficiency by adding new features.

The impact of klotho gene polymorphisms on urinary tract stone disease.

OBJECTIVES: To investigate the effect of klotho gene and ß-glucuronidase activity on stone formation in patients with urinary tract stone disease (UTSD). METHODS: A total of 103 patients with UTSD and 102 controls with no specific urolithiasis history were enrolled into the study. G395A and C1818T polymorphisms of klotho gene were analyzed with PCR method. Serum levels of calcium and phosphorus and 24-h urine levels of ß-glucuronidase activity, calcium and phosphorus levels were measured biochemically. RESULTS: A total of 103 of patients were male (50.2 %) and 102 were female (49.8 %) (p 0.945). Twenty-four-hour urine levels of calcium were significantly higher in UTSD group, whereas no difference was observed in phosphorus levels (p < 0.001, p 0.074, respectively). As for the G395A polymorphism, type of GG was significantly higher in the patient group compared to the controls (p = 0.02), while GA genotype was significantly higher in the controls (p = 0.001). There was no significant difference in F352V and C1818T polymorphism between the patient and control groups. ß-glucuronidase activity was slightly lower in the patient group without significance (p 0.932).When patients with GG genotype and the rest were compared, there were no significant difference in all parameters. CONCLUSIONS: Any polymorphism altering the function of klotho gene may result with stone formation. We found that there are more GG sequences of G395A gene in patients with UTSD. That may be a polymorphism of klotho gene which results with stone formation. Further studies with more patients should be accomplished which are combining the genetic and epigenetic factors associated with urolithiasis and klotho gene to enlighten the etiology of this disease.

Investigation of key miRNAs and target genes in bladder cancer using miRNA profiling and bioinformatic tools.

Despite the association of several miRNAs with bladder cancer, little is known about the miRNAs' regulatory networks. In this study, we aimed to construct potential networks of bladder-cancer-related miRNAs and their known target genes using miRNA expression profiling and bioinformatics tools and to investigate potential key molecules that might play roles in bladder cancer regulatory networks. Global miRNA expression profiles were obtained using microarray followed by RT-qPCR validation using two randomly selected miRNAs. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of three selected KEGG pathways were visualized by Cytoscape software. We finally gained 19 deregulated miRNAs, including 5 ups- and 14 down regulated in 27 bladder-cancer tissue samples and 8 normal urothelial tissue samples. The enrichment results of deregulated miRNAs and known target genes showed that most pathways were related to cancer or cell signaling pathways. We determined the hub CDK6, BCL2, E2F3, PTEN, MYC, RB, and ERBB3 target genes and hub hsa-let-7c, hsa-miR-195-5p, hsa-miR-141-3p, hsa-miR-26a-5p, hsa-miR-23b-3p, and hsa-miR-125b-5p miRNAs of the constructed networks. These findings provide new insights into the bladder cancer regulatory networks and give us a hypothesis that hsa-let-7c, hsa-miR-195-5p, and hsa-miR-125b-5p, along with CDK4 and CDK6 genes might exist in the same bladder cancer pathway. Particularly, hub miRNAs and genes might be potential biomarkers for bladder cancer clinics.

The Most Predictive Red Flags for Suspecting Cardiac Amyloidosis in Patients with Heart Failure with Preserved Ejection Fraction.

OBJECTIVE: Cardiac amyloidosis (CA) is a cardiomyopathy characterized by amyloid infiltration in the myocardium. Transthyretin cardiac amyloidosis (TTR-CA), commonly presenting as heart failure with preserved ejection fraction (HFpEF), was the focus of our study, which aimed to identify red flags that heighten suspicion of CA in HFpEF patients. METHODS: We prospectively included patients diagnosed with HFpEF. All patients were assessed for TTR-CA red flag features, cardiac and extra-cardiac, as outlined in the 'Diagnosis and Treatment of Cardiac Amyloidosis: A Position Statement of the European Society of Cardiology.' Technetium-99m pyrophosphate (99mTc-PYP) cardiac scintigraphy was performed in 167 HFpEF patients suspected of having TTR-CA. Patients testing positive and negative for TTR-CA were compared based on these red flag features. RESULTS: Out of 167 HFpEF patients, 19 (11.3%) were diagnosed with TTR-CA. In the TTR-CA group, 17 (89.5%) patients were 65 years or older. The presence of three or more red flags differentiated the TTR-CA positive and negative groups (P = 0.040). Features such as low voltage and pseudo infarct patterns were more prevalent in the TTR-CA group (P < 0.001 and P < 0.048, respectively). Left ventricular global longitudinal strain (LV-GLS) was lower in the TTR-CA positive group (P < 0.001). Multivariate analysis identified four variables-older age, pseudo infarct pattern, low/decreased QRS voltage, and LV-GLS-as strong, independent predictors of TTR-CA, with significant odds ratios (ORs) of 7.8, 6.8, 16.9, and 1.2, respectively. CONCLUSION: In this study, TTR-CA etiology occurs in approximately one in every ten HFpEF patients. The presence of three or more red flags increases the likelihood of TTR-CA. Older age, pseudo infarct pattern, low/decreased QRS voltage, and reduced LV-GLS are the most significant red flags indicating TTR-CA in HFpEF patients.

Early-onset Chronic Keratitis as the First Presenting Component of Autoimmune Polyendocrinopathy Syndrome Type 1 (APS-1): A Case Report and Review of the Literature.

Autoimmune polyendocrine syndrome type 1 (APS-1), also referred to as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare monogenic autosomal recessive autoimmune disease. It is caused by mutations in the autoimmune regulator (AIRE) gene. APS-1 is diagnosed clinically by the presence of two of the three major components: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and primary adrenocortical insufficiency. A 3.3-year-old girl was presented with a carpopedal spasm to the pediatric emergency clinic. She had a history of recurrent keratitis, and chronic candidiasis as urinary tract infections and oral thrashes. Hypoparathyroidism (HPT) was diagnosed based on low serum concentrations of calcium and parathyroid hormone and elevated serum concentrations of phosphate, and treatment with calcium and calcitriol supplementation was started. Genetic testing revealed homozygosity for nonsense c.769C>T (p.R257X) mutation in exon 6 in the AIRE gene which was reported previously. At the age of 5.6 years, she was presented with an adrenal crisis, and treatment with hydrocortisone and fludrocortisone was started. The reported case highlights that unexplained chronic keratitis in children may be the first and most severe component of this syndrome. The classic triad of APS-1 may also appear in the first decade of life.

Genetic Polymorphism on Chromosome 4q25 (rs17570669) May Predict Recurrence After Successful Electrical Cardioversion in Patients with Persistent Atrial Fibrillation.

OBJECTIVE: Direct current electrical cardioversion (DCCV) is an effective rhythm-control option for patients with atrial fibrillation (AF). Despite initial success, a high recurrence rate remains a significant challenge. There is limited data on the genetic predictors of AF recurrence following successful DCCV. In this study, we aimed to evaluate whether 11 single nucleotide polymorphisms (SNPs) previously associated with AF are also linked to recurrence after DCCV in the Turkish population. METHODS: Seventy-five patients with persistent AF, who achieved stable sinus rhythm following DCCV, were included in the study. The patients were prospectively monitored for the onset of AF recurrence. Clinical characteristics and SNPs were analyzed and compared between patients who experienced recurrence and those who did not. RESULTS: The average age of the patients was 61.9 ± 11.5, and 33 (44%) were female. Over an average follow-up period of 17.0 (11.0-25.0) months, AF recurrence was observed in 38 patients (50.7%). A SNP in the PITX2 gene (rs17570669) (OR: 9.00, 95% Confidence Interval (CI): 1.28-63.02) and another in the ZFHX3 gene (rs2106261) (OR: 8.96, 95% CI: 1.03-77.66) were notably associated with AF recurrence in the additive model (P = 0.027 and 0.047, respectively). Multivariate Cox regression analysis revealed that the rs17570669 SNP was the sole independent predictor of AF recurrence (Hazard Ratio (HR): 3.59, 95% CI: 1.05-12.21, P = 0.040). CONCLUSION: The SNP in the paired-like homeodomain 2 (PITX2) gene (rs17570669) emerges as an independent predictor for AF recurrence after successful electrical cardioversion.

Screening of Mutations in Maturity-onset Diabetes of the Young-related Genes and RFX6 in Children with Autoantibody-negative Type 1 Diabetes Mellitus.

Objective: Maturity-onset diabetes of the young (MODY) is the most common type of monogenic diabetes. To date, mutations have been identified in 14 different genes of patients with a clinical diagnosis of MODY. This study screened mutations in 14 MODY-related genes and the regulator factor X6 (RFX6) gene in children. Materials and Methods: The presence of clinical features of MODY and negative results for three autoantibody markers of T1DM in children and adolescents were used as inclusion criteria for genetic testing. The screening panel for next-generation sequencing included 14 MODY-related genes (GCK, HNF4A, HNF1A, HNF1B, PDX1, NEUROD1, KLF11, CEL, PAX4, INS, BLK, ABCC8, KCNJ11, and APPL1) and the RFX6 gene. Results: Twenty-four different variants in MODY-related genes were identified in 49 children diagnosed with autoantibody-negative type 1 diabetes mellitus (T1DM). A 12 variants were classified as P/LP while 12 were interpreted as variant of unknown significance (VUS). Nine of the pathogenic or likely pathogenic variants were found in GCK, two in HNF1B, and one in ABCC8. Three variants were novel, and one was a de novo variant. All of the variants, except one, showed heterozygotic inheritance. Conclusion: This study screened mutations in the 14 MODY-related genes and the regulatory factor X6 (RFX6) gene in Turkish children diagnosed with autoantibody-negative type 1 diabetes mellitus (T1DM). The frequencies of the MODY subtypes differed from previous reports. Although GCK-MODY was the most frequent mutation in Turkish children, similar to previous studies, the second most prevalent MODY subtype was HNF1B-MODY. This study also established three additional novel mutations in different MODY genes.

Genetic Investigations in Turkish Idiopathic Pancreatitis Patients Show Unique Characteristics.

BACKGROUND/AIMS: Pancreatitis is one of the leading causes of digestive system-related hospital admissions, and it has a genetic background in a considerable portion of the patients. In this study, we aimed to investigate the genetic risk factors of idiopathic pancreatitis in Turkish patients and the contribution of copy number variations to the pathogenesis. MATERIALS AND METHODS: Idiopathic pancreatitis is defined as failure to detect risk factors despite comprehensive clinical assessments. Next-generation sequencing and multiple ligand-dependent probe amplification of PRSS1, SPINK1, CTRC, and CFTR were performed. For further genotype-phenotype correlations, patients were also questioned for the age of onset, family history, and pancreatic divisum. RESULTS: A total of 68 idiopathic pancreatitis cases were enrolled. Variants with potential clinical significance of PRSS1 were identified in 13.4%, SPINK1 in 6.3%, CTRC in 4.7%, and CFTR in 26.5% of the patients. No copy number variants were seen in any of these genes. At least 7.4% of the participants had complex genetic etiology involving 2 genes. CONCLUSIONS: At least 42.6% of the participants had a potential genetic risk factor. Five novel genetic variants were identified, and distinctive genetic risk factors of Turkish population were shown. The results showed that genetic etiology was frequent in pancreatitis and it was even more prominent in patients with early-onset disease. Considering that genetic risk factors may be informative for decisionmaking in the treatment options in addition to providing extensive prognostic value and familial genetic consultation; clinicians need to be more eager to offer genetic tests to pancreatitis patients.

Conventional and molecular cytogenetic analyses in Turkish patients with multiple myeloma.

OBJECTIVE: Multiple myeloma (MM) is characterized by the accumulation and proliferation of malignant plasma cells, secreting monoclonal immunoglobulins and genetic abnormalities in MM have implications for disease progression and survival. In the present study, we investigated the frequency of chromosomal abnormalities (CA) in Turkish patients with MM, using interphase FISH and CC and evaluated the relationship between the rearrangements detected, prognosis and stage of disease. MATERIAL AND METHODS: We performed conventional cytogenetic and FISH studies in 50 patients to detect chromosome anomalies associated with MM. FISH probes were used to detect 13q14, 13q34, 17p13 deletions, IGH rearrangements, and monosomy and/or trisomy of chromosomes 5, 9, and 15. RESULTS: CC studies could be performed in 32 of 50 cases and five patients (15.6%) showed chromosomal aberrations while 27 (84.3%) had normal karyotypes. By FISH, eighteen percent (9/50) of cases were found to be normal for all parameters evaluated. Eighty-two percent (41/50) of the patients were positive for at least one abnormality. Chromosome 13 anomalies were detected in 54% (27/50) of cases. The second most common aberration observed is chromosome 15 aberrations (50%). CONCLUSION: Median survival rate was shorter in patients with one of the abnormalities including chromosome 13 aberrations, IGH rearrangements or P53 deletions. Chromosome 15 aberrations were significantly higher in patients with stage III disease (p=0.02). We conclude that FISH studies should be performed in conjunction with conventional cytogenetic analysis for prognosis in multiple myeloma patients.

Spectrum of PAH gene mutations and genotype-phenotype correlation in patients with phenylalanine hydroxylase deficiency from Turkey.

OBJECTIVES: The aim of our study was to define the genotype-phenotype correlations of mutations in the PAH gene among the Turkey's Central Anatolian region. METHODS: Demographic characteristics of 108 patients with hyperphenylalaninemia (HPA) and 94 patients whose diagnosis was confirmed by PAH gene analysis (Sanger DNA Sequence Analysis and Next-Generation Sequencing) were determined retrospectively. Blood phenylalanine levels were analyzed using the high-performance liquid chromatography method. RESULTS: Mild HPA-not-requiring-treatment (NT) was found in 50.9% of the patients, and a classical phenylketonuria (PKU) phenotype was found in 25.9%. Forty-seven types of variants were identified. The predominant variants were p.Ala403Val (9.9%), p.Ala300Ser (9.4%), and c.1066-11G>A (splicing) (9.4%). Missense mutations accounted for 68% of mutations and attenuated the clinical impact; splice variations were found in 14.8% of cases with severe features. The p.Thr380Met allele was specific to the mild HPA-NT group. The c.1066-11G>A (splicing) allele was associated with classical PKU, whereas the p.Arg408Trp allele was linked to severe symptoms. Three variations of unknown clinical significance were discovered: c.706+4A>T (splicing), c.843-5T>C (splicing), and p.Thr323=. Of these variants, the patient who was homozygous for the c.843-5T>C (splicing) allele related to the classical PKU phenotype. 70% of the patients who underwent tetrahydrobiopterin (BH4) test were responsive. Phenotypes that responded to BH4 treatment were mostly mild phenotypes. CONCLUSIONS: The PAH genotype is the main factor that determines the phenotype of PKU. Establishing the relationship between the identified genetic mutations and phenotypic characteristics will provide very important data for each patient in terms of the specific management style.

The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study)

Objective: Chronic myeloid leukemia (CML) is a clonal hematologic disorder characterized by t(9;22) translocation, in which cytogenetic aberrations can occur in Ph(+) and (-) clones. These aberrations develop due to clonal evolution as well as treatment and they have prognostic significance. They are grouped as major and minor route anomalies in terms of their effects on prognostic parameters, such as treatment response, overall survival (OS), disease stage, complete cytogenetic response (CCyR), and major molecular response (MMR). It is stated that major route anomalies have unfavorable prognostic effects compared to minor route anomalies. We aimed to investigate the frequency and prognostic effects of cytogenetic anomalies detected in Ph(+) and (-) clones. Materials and Methods: In this study, we retrospectively analyzed the cytogenetic results of 450 patients diagnosed with CML between 2005 and 2020. Results: We detected cytogenetic aberrations in Ph-positive and negative clones in 41 of 450 patients. The most common anomalies were trisomy 8 (+8), additional Ph chromosome (+Ph), and loss of chromosome Y. Rarely, aneuploidy of the Y chromosome, dup (22), +11, and +6 were seen in CML patients. We observed that these identified aberrations negatively affected MMR and CCyR, and generally resulted in changing imatinib treatment for second-generation tyrosine kinase activity inhibitors. Our results are compatible with the literature. Conclusion: We suggest that cytogenetic aberrations detected in Ph(+) and (-) clones should be a warning sign in terms of treatment and require close observation. The use of cytogenetic methods for the identification of these anomalies is also important.

IL-15 Gene Polymorphism in Celiac Disease Patients and Their Siblings.

BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathy characterized by lifelong gluten intolerance. Interleukin-15 (IL- 15) is a proinflammatory cytokine that is considered a key component in the immune reaction triggered by gluten. Our aim of this study was to evaluate the influence of IL-15 gene polymorphisms on CD development and clinical presentation. METHODS: The study was enrolled-with 90 CD patients (49 female/41 male, median years of age 11), their 38 siblings (20 female/18 male, median years of age 8), and 99 healthy controls (66 female/33 male, median years of age 13). Their demographic findings, symptoms, and signs histopathological grade, Human Leukocyte Antigen (HLA) types were recorded. IL-15 gene polymorphisms rs2857261, rs10519613, and rs1057972 were analyzed through PCR. RESULTS: There was a significantly higher frequency of GG genotype in rs2857972 polymorphisms and TT genotype in rs1057972 polymorphisms in celiac families compared to controls [41% vs. 23% (P = .0008), 36% vs. 11% (P = .001), respectively]. Without considering their HLA status, there was not any difference between celiacs and healthy siblings. However, when stratified according to their HLADQ2 status, rs2857972 GG polymorphism was 1.5 times prominent in celiacs than siblings at homozygous state, whereas rs1057972 TT genotype was found to be 2.5 times prominent in celiac siblings at heterozygous state. There was no association between these polymorphisms and clinical presentation. CONCLUSION: rs2857972 GG and rs1057972 TT variants of IL 15 are more prominent in celiac families than controls. However, the impact of IL-15 gene polymorphism on CD development is dependent on HLADQ2 status.

Association of eleven single nucleotide polymorphisms with refractive disorders from Eskisehir, Turkey.

AIM: To investigate relationship between refractive errors and eleven single nucleotide polymorphisms (SNPs) in HGF, GC, MFN1, GNB4, and VDR genes in Turkish population. METHODS: A group of 212 participants with myopia (n=91), hyperopia (n=45), and emmetropia (n=76) were investigated in this study. SNPs in HGF, GC, MFN1, GNB4 and VDR genes were studied by SnapShot technique. RESULTS: The patients in this study consists of 47 female/44 male (age: 23.47±4.30) patients with myopia, 20 female/25 male (age: 31.20±8.02) with hyperopia and 33 female/43 male (age: 25.22±6.60) with emmetropia. The genotype distribution of the rs7618348 polymorphism, which was the only statistically significant one between myopia and emmetropia group. The genotype distribution of the rs3819545, rs3735520, rs7041, and rs2239182 polymorphisms, which were statistically significant between hyperopia and emmetropia groups. CONCLUSION: The importance of genetic predisposition to refractive errors with respect to etiology of the disease is revealed. It is known that polymorphism studies may differ because of genetic diversity among populations so larger cohort studies are required in different populations to enlighten the etiology of the refractive errors.

A pediatric BAL case with double Ph chromosomes and trisomy 5.

Biphenotypic acute leukemias (BAL) are known as a type of leukemia involving cells with myeloid and along with lymphoid origin, in which genomic changes are detected. It has been stated that the most common genomic changes in BAL are t(9;22) and the translocations of the 11q23 region, these anomalies cause poor prognostic effects. We detected trisomy 5 (+5) in addition to the double Ph chromosome in a case where we investigated the genomic changes using molecular and conventional cytogenetic methods. Bone marrow transplantation was planned due to the poor response to prednisone. According to the information we have obtained, our report will be the first article to discuss the aberrations found in addition to the Ph chromosome in BAL and the effect of these aberrations on prognosis. However, the double observation of the Ph chromosome, which has a poor prognostic effect, is expected to affect the prognosis more negatively, this case will contribute to the literature in terms of trisomy 5. We think that more case reports are needed to reveal the anomalies and their prognostic significance in BAL.

A new four-way complex translocation variant involving the t(8;5;21;4)(q21;q13,q22,q31) and the relocalization of AML1/ETO fusion gene.

In acute myeloid leukemia, t(8;21) detected with a frequency of 10% is associated with good prognosis. However, variant t(8;21) is observed in 4% of these cases, and although the prognostic effects of these variant translocations have not been clearly revealed, there are findings that they affect the prognosis poorly. Here, we report on a 39 years old man, detected 4-way varyant t(8;21) which include relocalization of RUNX1/RUNX1T1 fusion gene, and loss of Y chromosome. RT-PCR also confirmed RUNX1/RUNX1T1 fusion transcript. Additionally, D820G and N822K mutations on KIT gene and mut B on NMP1 gene were detected. A complete remission could not achieved after first chemotherapy treatment. Due to primary resistance and variant of t(8;21), stem cell transplantation was performed. The variant translocation we have reported is unique and also the case is the second case that was reported in the literature in terms of the relocation of the AML1/ETO fusion gene. Since c-KIT mutations and LOY were also observed, it is not possible to predict the prognosis. To highlight the importance of variant translocations and relocalization of fusion gene, more cytogenetic and molecular data are needed.

The relationship of retinopathy of prematurity with brain-derivated neurotrophic factor, vascular endotelial growth factor-A, endothelial PAD domain protein 1 and nitric oxide synthase 3 gene polymorphisms.

BACKGROUND: In addition to risk factors such as low birth weight and uncontrolled oxygen therapy, genetic predisposition is also thought to play a role in the development of retinopathy of prematurity (ROP). In our study, we aimed to analyze single-nucleotide polymorphisms (SNPs) in VEGFA, EPAS1, BDNF and NOS3 genes in infants who develop ROP. MATERIALS AND METHODS: Seventy-five mild-moderate and 73 severe ROP cases were included in this study. Eleven different SNPs regions that located in VEGFA, EPAS1, BDNF and NOS3 genes were analysed by SnapShot technique and compared between two groups by the multiple logistic regression analysis. RESULTS: Statistically significant results were obtained in 8 of the 11 SNPs. It was observed that the excess of mutant alleles in four (VEGFA rs2010963 and rs3025039, EPAS1 rs13419896, NOS3 rs2070744) of these regions increased ROP severity and treatment requirement (p < .001, p < .001, p = .022, p = .004, respectively) while the excess of mutant alleles in the other four regions (VEGFA rs833061, BDNF rs7929344, EPAS1 rs1867785 and rs1868085) showed that ROP severtiy was milder and eliminated the need for treatment (p < .001, p = .019, p = .017, p = .017, respectively). CONCLUSIONS: Considering the results of our study, it was seen that besides the known environmental and demographic factors in ROP pathogenesis, genetic predisposition also had an effect on the clinic and course of ROP. Polymorphisms of VEGFA rs2010963 and rs3025039, EPAS1 rs13419896, NOS3 rs2070744 were found to be associated with severe ROP. More studies involving different populations cases are needed to confirm these findings and enlighten the etiology of ROP.

Genetic variants associated with atrial fibrillationand long-term recurrence after catheter ablation for atrialfibrillation in Turkish patients.

OBJECTIVE: Genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) are associated with atrial fibrillation (AF) and can predict AF recurrence after catheter ablation in different populations. However, there exists no such data for the Turkish population. We aimed to investigate whether 11 SNPs in the PITX2, ZFHX3, EPHX2, CAV1, TBX5, TGF-1, and SCN10A were related to AF and whether these SNPs can predict long-term atrial tachyarrhythmia (ATa) recurrence after pulmonary vein isolation (PVI) for AF in Turkish patients. METHODS: A total of 245 consecutive patients with non-valvular AF (44.9% men, mean age: 60.2±13.2 years, 65.3% paroxysmal AF) and 50 age- and sex-matched controls were included in this analysis. The clinical features and genetic variants were compared between the 2 groups. Of the 245 patients, 128 who underwent PVI with second-generation cryoballoon were further examined for long-term recurrence after the procedure. RESULTS: Four SNPs in PITX2 were significantly associated with AF (rs10033464_T: OR 3.29, 95%CI: 1.38-7.82, p=0.007; rs6838973_T: OR 3.06, 95% CI 1.36-6.87, p=0.007; rs3853445_C: OR 2.84, 95%CI: 1.27-6.36, p=0.011; rs17570669_T: OR 4.03, 95% CI: 1.71-9.51, p=0.001). Among these patients who underwent PVI, one locus in CAV1 (rs3807989_G: OR 4.50, 95% CI 1.04-19.31, p=0.043) and early recurrence (OR: 8.06, 95% CI: 2.12-30.55, p=0.002) predicted long-term AF recurrence after catheter ablation. CONCLUSION: Significant associations exists between 4 SNPs in PITX2 and AF (rs10033464, rs6838973, rs3853445, and rs17570669) in Turkish patients. In addition, 1 genetic variant in CAV1 (rs3807989) and early recurrence can predict long-term ATa recurrence after catheter ablation.