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Background Following the discovery that fetal DNA originates from the trophoblastic cells of the placenta, the contribution of the cell-free DNA test in placenta-related obstetric complications has begun to be investigated. Compared to uncomplicated pregnancies, higher fetal fractions were detected in placenta accreta spectrum and placenta previa, which are among placenta-related obstetric complications. However, this data applies only to advanced gestational weeks. Aim To investigate the possible predictive value of fetal fraction in cell-free DNA tests in pregnancies with placenta previa and placenta accreta spectrum in early gestational ages. Materials and Methods This study was conducted in women who were screened via cell-free DNA tests for common aneuploidies in the first and second trimester and subsequently diagnosed with placenta previa or placenta accreta spectrum. After the diagnosis was confirmed with a C-section, fetal fractions were retrospectively compared to a control group with a history of an uncomplicated C-section who were also previously screened by cell-free DNA test. Results The median and interquartile range (IQR) of fetal fractions for placenta previa (n=19), placenta accreta spectrum (n=7), and control groups (n=85) were 8.1 (6–10), 6.8 (6.7–10.7), and 7.1 (4.7–9.65), respectively. No statistically significant difference was observed among the three groups in terms of fetal fractions (p=0.587). Conclusions According to our data, we did not observe any relationship between placental invasion abnormalities vs. control group or placenta previa vs. control group using the fetal fractions of the cell-free DNA test. Furthermore, we could not confirm a predictive role and/or any additional clinical contribution. We believe that future studies focusing on placental mRNA might be more helpful than cell-free fetal DNA testing.

Objectives Nephrocalcinosis is associated with conditions that cause hypercalcemia and the increased urinary excretion of calcium, phosphate, and/or oxalate. A monogenic etiology is found in almost 30% of childhood-onset nephrocalcinosis which is also a common manifestation of primary hyperparathyroidism. We discuss a child with nephrocalcinosis and features mimicking primary hyperparathyroidism. Case presentation A 7-year-old girl presented with nephrocalcinosis. Hypercalciuria, hyperphosphaturia, mild hypercalcemia, hypophosphatemia and elevated parathyroid hormone levels along with normal serum creatinine and absence of hypokalemic alkalosis suggested primary hyperparathyroidism. However, she was ultimately diagnosed with Bartter syndrome type 2 based on the presence of homozygous pathogenic variation in KCNJ1gene. Conclusions This is the second reported case of late-onset Bartter syndrome type 2 without hypokalemic alkalosis. Patients with Bartter syndrome may present with high parathyroid hormone levels and hypercalcemia in addition to hypercalciuria. Thus, the present case suggests that the KCNJ1 gene should be included in genetic analysis even in older children with isolated nephrocalcinosis.

Background: Osteogenesis imperfecta (OI), is a heritable, heterogeneous connective tissue disorder, characterized by fragile bones. There are conflicting results about genotype-phenotype correlations and efficiency of bisphosphonate treatment in this disorder. Aim: We aimed to evaluate the clinical, genetic characteristics, and long-term follow-up results of children and adolescents with OI. Materials and methods: A two-center retrospective study was conducted using demographic, clinical, and genetic data obtained from the medical records of the patients. Results: Twenty-nine patients (62% male, median age; 3.6 years) with OI diagnosis from 26 families were included in the study. Thirteen different variants (nine were novel) were described in 16 patients in COL1A1, COL1A2, and P3H1 genes. Our siblings with homozygous P3H1 variants had a severe phenotype with intrauterine and neonatal fractures. Twenty-two patients were treated with bisphosphonates (17 of them with pamidronate, five with alendronate) with a median duration of 3.0 (1.6-4.8) years. Eleven patients (50%) suffered from fractures after the treatment. Haploinsufficiency variants in COL1A1 caused a milder skeletal phenotype with less fracture count and better treatment outcomes than structural variants. When compared with the anthropometric measurements at the initial diagnosis time, height Z-scores were lower on the last clinical follow-up (p = 0.009). Conclusions: We could not find an obvious genotype-phenotype correlation in Turkish OI patients with COL1A1 or COL1A2 variants. Treatment with pamidronate was effective in reducing fracture counts, without any long-term adverse effects.

Objective: Non-invasive prenatal testing (NIPT) and fetal fraction (FF) are shown to be affected by various factors like maternal characteristics or medications. Recently medications are now undergoing evaluation as influencing factors. Still no data are presented on the relation between levothyroxine, NIPT and FF results. The study's aim is to assess the effect of levothyroxine sodium on the FF. Material and Methods: This retrospective case control study was conducted with medical records of pregnant women who underwent NIPT between 2016-2020 at our institution. Women with multiple gestation, body-mass index >= 25, abnormal fetal karyotype, pregnancy with assisted reproductive techniques, those without FF report and non-euthyroid patients were excluded. The pregnant euthyroid women included in the study were divided into two groups: using and not using levothyroxine. Maternal characteristics, FF of the NIPT, TSH, FT4 values and levothyroxine dosing were noted and compared between the two groups. Results: Data were collected from 51 pregnant women using levothyroxine and 102 pregnant women who did not. There was no difference in demographic characteristics, also no significant difference was shown in TSH and FT4 between the groups (p=0.180, p=0.920). The mean FF level in pregnant women using levothyroxine is lower, but the situation did not reach statistical significance (p=0.070). Conclusion: The knowledge of relation between FF and medications is largely based on very limited data. This is the first report of assessing levothyroxine effect on FF percentage in NIPT. Levothyroxine sodium was not confirmed to be associated with any significant change in the FF.

There are numerous causes, such as environmental factors, medications, endocrine disorders, and genetic factors, that can lead to obesity. However, severe early-onset obesity with abnormal feeding behavior, mental retardation, dysmorphic features, organ-specific developmental abnormalities, and endocrine disorders suggest a genetic etiology. Mutations in genes related to the leptin-melanocortin pathway play a key role in genetic obesity. This pathway controls hypothalamic regulation of food intake. A few cases have been reported to have mutations in leptin (LEP) or leptin receptor (LEPR) genes. The cases had severe early-onset obesity, hyperphagia, and additional features, such as altered immune function, hypogonadism, and hypothyroidism. We present a 3-year-old male patient with severe early-onset obesity whose genetic analysis revealed a homozygous, novel, and pathogenic variant (c.1603+2T>C) in LEPR.

Background: Lynch syndrome is an inherited cancer disorder that causes an increased lifetime risk of various types of cancers. Endometrial cancer is the most common extracolonic cancer in Lynch syndrome. Guidelines recommend that patients with endometrial cancer younger than 50 years of age should be evaluated for Lynch syndrome. Molecular analysis of the mismatch repair genes and EPCAM gene is required for a definitive diagnosis of Lynch syndrome. Aims: To report the mutation analysis of mismatch repair genes using targeted next-generation sequencing in endometrial cancer diagnosed patients

This study presents a nonamplification-based nucleic acid assay for the detection of single-nucleotide polymorphism (SNP) associated with familial Mediterranean fever (FMF) besides polymerase chain reaction (PCR)-based methodologies. The major objective is to show the potential of the proposed assay for rapid screening of FMF in a Mediterranean region of 400 million population. The assay relies on binding difference of specially designed wild and mutant primers to the target genomic DNA, followed by determination of unbound primers by quick titration of a cationic polythiophene reporter. The fluorescent reporter exhibits signal transition from 525 to 580 nm in the presence of unbound primers, and it correlates the binding affinity of label-free primers to the homozygous wild and mutant genomes. As a proof of concept, 26 real samples are studied relying on the ON and OFF fluorescence signals of the cationic polythiophene reporter. The results are analyzed by principal component analysis (PCA), which provides clear separation of healthy and patient individuals. The further analysis by support vector machine (SVM) classification has revealed that our assay converges to 96% overall accuracy. These results support that the PCR-free nucleic acid assay has a significant potential for rapid and cost-effective screening of familial Mediterranean fever.

Warburg micro syndrome (WARBM) is a rare autosomal recessive disorder characterized by microcephaly, cortical dysplasia, intellectual disability, ocular abnormalities, spastic diplegia, and microgenitalia. WARBM has 4 subtypes arising from pathogenic variants in 4 genes (RAB18, RAB3GAP1, RAB3GAP2, and TBC1D20). Here, we report on a patient with a homozygous pathogenic c.665delC (p.Pro222HisfsTer30) variant in the RAB3GAP1 gene identified by whole-exome sequencing (WES) analyses. Only his father was a heterozygous carrier, and homozygosity mapping analysis of the WES data revealed large loss-of-heterozygosity regions in both arms of chromosome 2, interpreted as uniparental isodisomy. This uniparental disomy pattern could be due to paternal meiosis I nondisjunction because of the preserved heterozygosity in the pericentromeric region. This report provides novel insights, including a rare form of UPD, usage of homozygosity mapping analysis for the evaluation of isodisomy, and the first reported case of WARBM1 as a result of uniparental isodisomy.

ObjectiveTo investigate the possible predictive value of fetal fraction in the cell-free DNA (cfDNA) test in pregnancies with early- and late-onset fetal growth restriction (FGR).MethodsThis retrospective study comprised 247 women who were screened using the cfDNA test for aneuploidies during the first or second trimester and had deliveries at our institution from January 2016 to December 2019. The fetal fractions of women with early- (n = 14) and late-onset (n = 83) FGR and those with uncomplicated pregnancies (n = 150) were compared.ResultsThe median fetal fractions for the early-onset FGR, late-onset FGR, and control groups were 5.7 [interquartile range (IQR) 2.65], 7 (IQR 5), and 7.35 (IQR 3.65), respectively. The fetal fractions were significantly lower in the early-onset FGR group than in the late-onset FGR and control groups (P = 0.047 and P = 0.037, respectively). There was no difference in fetal fractions between the late-onset FGR and control groups (P = 1.00).ConclusionAs a placenta-related disease, early-onset FGR had lower fetal fractions in the cfDNA test than uncomplicated pregnancies. For clinical use, lower fetal fractions can contribute as a biomarker for screening asymptomatic women for possible placenta-related diseases, such as early-onset FGR. However, more studies are needed to define the “lower” limit.

INTRODUCTION Brain metastasis prevalence is higher in patients with positive epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) and C-ROS oncogene 1 (ROS-1) fusion change in lung adenocarcinoma. OBJECTIVES The purpose of our study is to investigate the relation between the genetic change type and the initial distant metastasis in stage IV lung adenocarcinoma patients with genetic changes. METHODS The study was conducted between January 2007 and December 2018 in a retrospective fashion with patients who had lung cancer diagnosed as stage IV adenocarcinoma. The relation between genetic mutation change (EGFR, ALK or ROS-1) and distant metastasis was analysed. RESULTS A total of 845 patients were included in the study. The median age was 62 (28-88). It was determined that lung and pleura metastases were more frequent at a significant level in patients with positive EGFR mutation (P = 0.032, P = 0.004, respectively). In patients with positive ALK fusion change, pleura metastasis was determined to be more frequent (P = 0.001). Multiple metastases were determined to be significantly more in patients with positive ALK fusion change than single metastasis (P = 0.02). CONCLUSION In patients with EGFR mutant lung adenocarcinoma, lung and pleura metastasis is more frequent and pleura metastasis is more frequent in ALK positive adenocarcinoma. Additionally, multiple organ metastases are higher in ALK positive lung adenocarcinoma.

The aim of this study was to evaluate the maternal and foetal factors affect higher cell-free DNA (cfDNA) levels and to investigate a possible relationship between high cfDNA levels and adverse perinatal outcomes. From a total of 4594 women who underwent non-invasive prenatal testing from January 2016 to March 2018 in our hospital, 112 women had high levels of cfDNA, which was not appropriate for testing. Maternal characteristics and perinatal outcomes were compared between patients with high levels of cfDNA and normal levels of cfDNA. Patients with high levels of cfDNA had greater risks than patients with normal cfDNA levels of pregnancy complications but no statistically significant difference was found. Patients with high cfDNA levels had higher foetal death rates with a statistically significant difference (9.8% versus 1.8%, p = .024). An increase in foetal death could be expected in patients with increased cfDNA levels; therefore, these patients should be carefully followed up during pregnancy.IMPACT STATEMENT What's already known about this topic? Most studies about cfDNA levels are focussed on the foetal fraction. There are new arguments about maternal health and cfDNA. It is known that autoimmune diseases as systemic lupus erythematosus (SLE) and maternal obesity increase cell turnover. There are also clinical studies suggesting a relationship between low molecular weight heparin therapy and the amount of cfDNA. What do the results of this study add? This is the first study evaluating the maternal and foetal biological factors affecting cfDNA concentrations and investigating the possible relationship between high cfDNA levels and adverse perinatal outcomes in patients with high levels of cfDNA compared to patients with normal levels of cfDNA. In the present study, it was found that an increase in foetal death could be expected in patients with higher cfDNA levels.

Background. Immunosuppression at the feto-maternal interface is crucial for a successful pregnancy outcome. Human leukocyte antigen-G (HLA-G) seems to be a major contributor to fetal tolerance. The HLA-G expression is seen in cytotrophoblasts and in maternal blood. Fetal HLA-G acts on decidual antigen-presenting cells (APCs), natural killers (NKs) and T cells. Recent findings revealed that defects in placentation and their consequences are associated with maternal HLA-G variants and their expression levels. Objectives. The objective of this article is to investigate the relationship between fetal HLA-G alleles and miscarriage, which has not been investigated to date. Material and methods. The present study includes 204 recurrent miscarriage (RM) cases who were admitted to our clinic between 2012 and 2016. Twenty-eight miscarriage products without maternal cell contamination and any known pathology were analyzed by HLA-G typing. In addition, 3' untranslated region (UTR) 14-base pair (bp) insertion/deletion polymorphism was also investigated by Sanger sequencing. Results. For our population, the most frequent HLA-G type was G*01:01, both in the study group (30.3%) and in the control group (47%). The study revealed that the G*01:04 allele was significantly associated with miscarriage (p = 0.007). The 3' UTR 14bp deletion was more frequent in the miscarriage group, but there was no significant correlation. Conclusions. HLA-G alleles seem to be related with miscarriage and should be considered in RM cases.

Objective: The aim of this study was to evaluate both the frequency of Asn680Ser polymorphism of follicle stimulating hormone receptor (FSHR) and whether this polymorphism is associated with polycystic ovary syndrome (PCOS) in a Turkish population. Patients and Methods: 100 patients with PCOS and 100 controls were recruited from Eastern Turkey. Venous blood samples were obtained for genetic study, hormone profile, glucose and insulin assays. Asn680Ser polymorphism of FSHR was analyzed by polymerase chain reaction (PCR) amplification and direct DNA sequencing. Two groups were compared for body mass index (BMI), modified Ferriman-Gallwey (mFG) score, fasting glucose, fasting insulin, insulin resistance, hormone and lipid status. Then, all patients were divided into subgroups for genotypes of FSHR polymorphism. These subgroups were also compared for these mentioned parameters. Results: The difference between women with PCOS and controls in allelic frequencies for Asn680Ser polymorphism of FSHR were not significant. When this single nucleotide polymorphism (SNP) at codon 680 was separately analyzed, no significant difference was found in the genotype frequency among the Asn680Asn, Asn680Ser, andSer680Ser subgroups. There were no significant differences in BMI, mFG score, levels of fasting glucose and fasting insulin, HOMA-IR, and also levels of FSH, luteinizing hormone, estradiol, prolactin, thyroid stimulating hormone, total testosterone among the PCOS patients carrying different genotypes of Asn680Ser polymorphism Conclusion: there is no association between Asn680Ser polymorphism of FSHR and PCOS in Turkish women from eastern provinces of Turkey. In addition, this SNP seems not to be associated with BMI, IR and PCOS-associated endocrine hormones.

Background Chromosomal microarray analysis is the first-tier test for the evaluation of developmental disabilities and congenital anomalies. In this report, we present CMA results of 971 patient and 301 parent samples. Materials and Methods Among 971 patient samples, 133 (13.6%) had pathogenic variants. Results While analyzing, an “in-house” variant database was also used besides other databases. Owing to this, we have found chance to report the most frequent benign variants in Turkish population. Conclusion With the additional data we acquired in this study, we also emphasized the high potential of CMA in revealing single gene disorders and novel gene-phenotype associations as well as copy number variations.

Aim: We aimed to share our genetic test results for SMA since 2001, and compare the commonly used screening and diagnostic methods for SMA.

Background Next‐generation sequencing (NGS) and discovery of fetal cell‐free DNA (cfDNA) in the maternal circulation render possible prenatal screening for trisomy 21 (Down syndrome), trisomy 18, trisomy 13, and sex chromosome aneuploidies. The approach is called “fetal cfDNA screening” and in contrast to noninvasive conventional serum screening, it provides the identification of 98%–99% of fetuses with Down syndrome. Methods Retrospective analysis of targeted noninvasive prenatal testing (NIPT) (Clarigo Test) pregnancies with moderate risk, which we have reported between 2016 and 2018 years is presented. Two separate laboratory workflows and NGS platforms are used for the same targeted NIPT analysis. Results In total, 4,594 pregnant women were investigated. Initial 3,594 cases are studied by MiSeq platform, the last 1,000 cases by NextSeq. Failure rate for MiSeq platform is 10.9% and for NextSeq is 8.7%. Automatically reported cases constitute 75% of the MiSeq group and 87% of the NextSeq group. Conclusions Targeted NIPT results suggest that MiSeq platform could be used for NIPT which would be an essential option particularly for laboratories with low sample flow. And, the NextSeq platform has easier wet lab process and also increased success rate in automatic reporting which is suitable for centers with high number of NIPT cases.

As in all living cells, cancer cells are evaluating is very important in the frames of tumor development and treatment. As in all evolutionary process, the environment of living cells has an important role. Tumor cells have an environment is called tumor microenvironment, affects the therapeutic response and clinical results. Tumor microenvironments involve various cell types, extracellular matrix substances that are in the niche of cancer cells. The microenvironment is not only important in tumorigenesis but it is effective on therapeutic efficacy. In this review, we carried out the interaction between non-small cell lung cancer and its microenvironment to point out the significance of the tumor environment.

EgeUn###, Exhaled breath is a source of volatile and nonvolatile biomarkers in the body that can be accessed non-invasively and used for monitoring. The collection of lung secretions by conventional methods such as bronchoalveolar lavage, induced sputum collection, and core biopsies is limited by the invasive nature of these methods. Non-invasive collection of exhaled breath condensate (EBC) provides fluid samples that are representative of airway lining fluids. Various volatile and nonvolatile biomarkers can be detected in volatile condensates, such as H2O2, nitric oxide, lipid mediators, cytokines, chemokines, DNA, and microRNAs. Studies have examined cell-freeDNA(cfDNA) in plasma samples from non-small-cell lung cancer patients, offering to new insights and fostering development of the liquid biopsy. However, few studies have examined cfDNA in EBC samples. This study examined whether EBC is an appropriate source of cfDNA using housekeeping-gene-specific primer probes and quantitative real-time polymerase chain reaction in healthy subjects. Ambient (room) air is contaminated with DNA, so caution is needed. Preliminary studies indicated that volatile biopsies are becoming an important diagnostic tool in lung cancer., Department of Scientific Research Projects of Dokuz Eylul University [KB.SAG.049]; Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [216S435, 216S591], Informed consent was obtained from all research subjects. The study was approved by the Ethics Committee of Ege University and was supported by grants from the Department of Scientific Research Projects of Dokuz Eylul University (Project no: 2017.KB.SAG.049) and the Scientific and Technological Research Council of Turkey (Project no: 216S435 and 216S591).

Objectives: We have no series report concerning genetic etiology of Alport Syndrome AS in our country. So, we aimed to investigate AS related pathogenic variants of COL4A3, COL4A4 and COL4A5 genes in index cases and their families who referred to our center.Patients and Methods: The study includes 32 subjects 17 index cases and their relatives who are investigated between years 2018-2019 by NGS targeting the coding regions of related genes. The test results and clinical findings of the cases are studied retrospectively.Results: By the presented study, 19 individuals identified to have COL4A3 and COL4A5 variations which could be important for the clinical management. In four cases, there are novel variants. In two cases, there are digenic variations. There is no clinically relevant variant in COL4A4 gene. The most frequent three mutations of COL4A5 gene reported in United States US are not determined in our study group.Conclusion: The diagnostic genetic tests of AS should be designed to include whole coding regions of COL4A3 and COL4A5 genes, not just for the frequently reported pathogenic variants. The cases without pathogenic variants by sequencing should be investigated for deletions/duplications of COL4A5 gene. Clinical findings of our cases with novel genetic variants are presented as a contribution to literature

Background: Lynch syndrome is an inherited cancer disorder that causes an increased lifetime risk of various types of cancers. Endometrial cancer is the most common extracolonic cancer in Lynch syndrome. Guidelines recommend that patients with endometrial cancer younger than 50 years of age should be evaluated for Lynch syndrome. Molecular analysis of the mismatch repair genes and EPCAM gene is required for a definitive diagnosis of Lynch syndrome. Aims: To report the mutation analysis of mismatch repair genes using targeted next-generation sequencing in endometrial cancer diagnosed patients

Introduction: About 80% of lung cancer cases are classified as “Non-Small Cell Lung Cancer (NSCLC)”. Case spesific, targeted therapies (precision medicine) are developed for advanced NSCLC. The main targets are the mutations of EGFR gene which are found in 10-30% of cases. Tyrosine kinase inhibitors (erlotinib, gefitinib, afatinib, osimertinib) are offered if the tumor has the mutations. At the 9-13th months of targeted tyrosine kinase therapy, drug resistance related EGFR T790M mutation may occur. Aim: Our goal is to identify the effect of liquid biopsy in the management of NSCLC and share the results of our genetic diagnosis center. Methods: We have examined 42 mutations of EGFR gene, in 114 NSCLC cases that referred to our center in 2017-2018. Plasma derived cell-free DNA (cfDNA) samples are used to identify 42 mutations of EGFR gene including exon 19 (Ex19del), exon 20 (T790M), exon 21 (L858R) variants by “Real-Time Quantitative PCR” (RT-PCR) method. Results: The EGFR mutations are found in 23 liquid biopsy cases (20%). Eleven of the cases (9.6%) have single sensitivity related mutation: Five cases have Ex19del, 4 cases have L858R, 2 cases have Ex20ins. In addition, one case has “Ex19del and G719X” together. The remaining 11 (9.6%) have the drug resistance related T790M mutation in addition to a sensitivity mutation: Six cases have “Ex19del ve T790M”, 4 cases have “L858R ve T790M”, 1 case has “L858R, S768I ve T790M”. The 11 cases with normal liquid biopsy result actually have a EGFR mutation in solid tissue biopsy. Conclusion: The liquid biopsy is successfully took its place in the identification of EGFR mutations of advanced NSCLC cases.

Background Maturity-onset diabetes of the young (MODY) is a common form of monogenic diabetes. Fourteen genes have been identified, each leading to cause a different type of MODY. The aims of this study were to reveal both known and novel variants in MODY genes in patients with MODY using targeted next generation sequencing (NGS) and to present the genotype-phenotype correlations. Methods Mutation analysis of MODY genes (GCK, HNF1A, HNF4A, HNF1B, ABCC8, INS and KCNJ11) was performed using targeted NGS in 106 patients with a clinical diagnosis of MODY. The variants were evaluated according to American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines recommendations. Results A total of 18 (17%) variants were revealed among all patients. Seven variants in GCK, six in HNF4A, four in HNF1A and one in ABCC8 genes were found. Eight of them were previously published and 10 of them were assessed as novel pathogenic or likely pathogenic variants. Conclusions While the most frequent mutations are found in the HNF1A gene in the literature, most of the variants were found in the GCK gene in our patient group using the NGS method, which allows simultaneous analysis of multiple genes in a single panel.

Triple negative breast cancer (TNBC), an agressive subtype accounts nearly 15 % of all breast carcinomas. Conventional chemotherapy is the only treatment modality thus new, effective targeted therapy methods have been investigated. Epidermal growth factor receptor (EGFR) inhibitors give hope according to the recent studies results. Also therapeutic agents have been tried against aberrant p53 signal activity as TNBC show high p53 mutation rates. Our aim was to detect the incidence of mutations/amplifications identified in TNBC in our population. Here we used sequence analysis to detect HER2 (exon 18-23), p53 (exon 5-8) mutations; fluorescence in situ hybridization (FISH) method to analyse EGFR/chromosome 7 centromere gene status in 82 immunohistochemically TNBC. Basaloid phenotype was identified in 49 (59.8 %) patients. EGFR amplification was noted in 5 cases (6.1 %). All EGFR amplified cases showed EGFR overexpression by immunohistochemistry (IHC). p53 mutations were identified in 33 (40.2 %) cases. Almost 60 % of the basal like breast cancer cases showed p53 mutation. Only one case showed HER2 mutation (exon 20:g.36830_3). Our results showed that gene amplification is not the unique mechanism in EGFR overexpression. IHC might be used in the decision of anti-EGFR therapy in routine practice. p53 mutation rate was lower than the rates reported in the literature probably due to ethnic differences and low sensitivity of sanger sequences in general mutation screening. We also established the rarity of HER2 mutation in TNBC. In conclusion EGFR and p53 are the major targets in TNBC also for our population.

Ring chromosome 13 is a rare genetic condition with an incidence of 1/58,000 in live births. Major clinical features of patients with ring chromosome 13 include growth and developmental retardation, microcephaly, facial dysmorphism, ambiguous genitalia, anal atresia, eye malformations, retinoblastoma, and hand, foot, and toe abnormalities. The severity of the phenotype depends on the amount of genetic material lost during ring chromosome formation. Here, we report 2 cases with ring chromosome 13 at either end of the phenotypic spectrum. (c) 2018 S. Karger AG, Basel

Objective: The aim of this study was to evaluate both the frequency of Asn680Ser polymorphism of follicle stimulating hormone receptor (FSHR) and whether this polymorphism is associated with PCOS in a Turkish population. Patients and Methods: 100 patients with PCOS and 100 controls were recruited from Eastern Turkey. Venous blood samples were obtained for genetic study, hormone profile, glucose and insulin assays. Asn680Ser polymorphism of FSHR was analyzed by polymerase chain reaction (PCR) amplification and direct DNA sequencing. Two groups were compared for body mass index (BMI), modified Ferriman-Gallwey (mFG) score, fasting glucose, fasting insulin, insulin resistance, and hormone and lipid status. Then, all patients were divided into subgroups for genotypes of FSHR polymorphism. These subgroups were also compared for these mentioned parameters. Results: The difference between women with PCOS and controls in allelic frequencies for Asn680Ser polymorphism of FSHR were not significant. When this single nucleotide polymorphism (SNP) at codon 680 was separately analyzed, no significant difference was found in the genotype frequency among the Asn680Asn, Asn680Ser, andSer680Ser subgroups. There were no significant differences in BMI, mFG score, levels of fasting glucose and fasting insulin, HOMA-IR, and also levels of FSH, LH, E2, PRL, TSH and TT among the PCOS patients carrying different genotypes of Asn680Ser polymorphism Conclusion: there is no association between Asn680Ser polymorphism of FSHR and PCOS in Turkish women from eastern provinces of Turkey. In addition, this SNP seems not to be associated with BMI, IR and PCOS-associated endocrine hormones.

Background/aim: QF-PCR has been used for more than 20 years. It is based on investigation of polymorphic short tandem repeats (STRs) and is widely used for prenatal rapid aneuploidy detection. Materials and methods: We report retrospectively our prenatal diagnosis results between January 2012 and May 2014 in Tepecik Training and Research Hospital Genetic Diagnostic Center. Prenatal diagnosis was recommended in 6800 high-risk pregnancies and 2883 patients agreed to invasive diagnosis. Chromosome analysis and QF-PCR were performed in all patients. Results: Normal results were reported in 2711 cases by fetal karyotyping and in 2706 cases by QF-PCR. Anomaly detection rates were similar for the two methods (5.09% for karyotyping and 4.02% for QF-PCR). Conclusion: QF-PCR is a fast and reliable prenatal diagnosis method in all indication groups and may be preferred as the sole prenatal investigation in patients without fetal ultrasonographic findings.

Ventriculomegaly (VM) is a marker of aneuploidy and warrants a detailed examination of fetal anatomy. Chromosomal abnormalities worsen the fetal and neonatal prognosis significantly and karyotyping of fetuses is critically important when accompanying anomalies are detected. Here, we report the genetic results of 140 fetuses with isolated and non-isolated VM detected during a second trimester ultrasound examination followed by invasive in utero diagnostic procedures for karyotyping. VM was diagnosed in seven (5%) fetuses with abnormal karyotype and the chromosomal abnormality incidence was higher in severe VM (6.8%) than mild (4.2%). Higher chromosomal abnormality rates were detected when VM was isolated (8.6%), rather than associated with any anomaly (3.8%). These results suggest that karyotype analysis should be offered to all patients with any degree of VM, regardless of its association with structural anomalies.

The aim of this study is to evaluate the frequency and types of associated anomalies with the results of ultrasonographic and postmortem examination and identify the necessity of prenatal karyotyping among fetuses with open neural tube defects (NTD). Fetuses diagnosed with NTDs between 2008 and 2012 were retrospectively analysed. A total of 167 fetuses that were prenatally karyotyped, terminated and examined at postmortem were evaluated. Associated anomalies were detected and classified by detailed ultrasonography and autopsy findings. In total, 57 fetuses (34.1%) had associated anomalies. Prenatal ultrasonography detected 73.1% of additional anomalies compared with autopsy. Three fetuses had chromosomal abnormalities with multiple additional anomalies. A complete anatomical survey and genetic evaluation is needed for the fetuses with NTDs. We found lower chromosomal abnormality rates but due to some factors specific to NTDs, ultrasonography may not be predictive as to whether the fetus is isolated or not. We still therefore also off er chromosome analysis in isolated cases.

ABS TRACT De ter mi na ti on of the ori gin of the mar ker chro mo so mes is very dif fi cult and requires ef fort. Eva lu a ti on of the mar ker chro mo so mes of the preg nancy lost tis su e co uld be the most dif fi cult one as the con ta mi na ti on with ma ter nal de ci du al cells comp li ca tes this pro cess. Con ven ti o nal cyto ge ne tic tech ni qu es and flu o res cen ce in si tu hybri di za ti on tech ni qu e or mo re ad van ced mo le cu lar tech ni qu es are pre fer red to de ter mi ne the ori gin of the se chro mo so mes. In this re port, the study for iden ti fi ca ti on of the ori gin of an abor ti on ma te ri al de ri ved from the pri mary tis su e cell cul tu re, with a 47,XX,+mar(15) kar yoty pe was pre sen ted, by using an ef fec ti ve al go rith mic ap pro ach which en ded with ge noty ping. The re sult of the ge noty ping was in for ma ti ve, sin ce the as su med abor ti on ma te ri al ac tu ally be lon ged to the mot her’s de ci du al tis su e. This bri ef study re minds the ef fi ci ent al go rith mic ap pro ac hes to the de ter mi na ti on pro cess of the mar ker chro mo so mes of the abor ti on ma te ri al.

Two common forms of autoimmune thyroid diseases are Graves' disease and Hashimoto's thyroiditis. Cytotoxic T lymphocyte antigen 4 (CTLA4) encoded by the CTLA4 gene on chromosome 2q33 plays a role in susceptibility to Graves' disease and is probably important also for Hashimoto's thyroiditis as well as for the other endocrine autoimmune disorders. The CTLA4 locus is the only nonhuman leukocyte antigen locus that has been found in association with Graves' disease repeatedly. Particularly, association of three polymorphic markers of CTLA4 gene, namely, C(-318) T, A49G, and (AT)n dinucleotide repeat, with Graves' disease was demonstrated in most of the population-based investigations. On the other hand, there are few studies to reveal the association of these markers with Hashimoto's thyroiditis. A49G polymorphism was proposed to be associated with Hashimoto's thyroiditis, and C(-318) T was suggested to be not associated. The patient groups consisted of 88 patients (10 males and 78 females; mean age: 14.5 +/- 3.2 years [4.6-21.0 years]) with a previous diagnosis of Hashimoto's thyroiditis and 112 euthyroid volunteers (51 males and 61 females; mean age: 14.1 +/- 2.9 years [5.2-18 years]). The frequency of A/G (A49G) genotype was high and statistically significant in patients with Hashimoto's thyroiditis in comparison with the control group. Although the frequency of C/T [C(-318) T] genotype is not significantly high in children with Hashimoto's thyroiditis according to the control group, the risk of Hashimoto's thyroiditis in A/G genotype group was 4.66 times greater than the group with A/A genotype. In this study, we documented that the A49G polymorphism might increase the susceptibility for Hashimoto's thyroiditis.

Bu yazıda, sol atriyum izomerizmi, heterotaksi sendromu ve tam kalp bloğu olan Meckel-Gruber sendrom’lu (MKS) bir fetüs sunuldu. Yirmi altı yaşındaki sağlıklı anne gebeliğinin 23. haftasında kliniğimize başvurdu. Fetüsün kalbi de içeren çok sayıda sistemik anomalisi vardı. Fötal ekokardiyografide horizontal karaciğer, sol yerleşimli mide ve azigos devamlılığı olan kesintili kaval veni vardı. Ayrıca apikal trabeküler ventriküler septal defekt, sol ventrikülden çıkan aorta ve pulmoner arter, pulmoner arter hipoplazisi, pulmoner kapak stenozu ve sol atriyum izomerizmi mevcuttu. Kalp hızı 46/dk idi ve üçüncü derece kalp bloğu ile uyumlu idi. Obstetrik ultrasonografisinde oksipital ensefalosel, iki taraflı polikistik böbrekler, yarık dudak, yarık damak ve polidaktiliyi içeren çok sayıda anomali saptandı. Perinatoloji konseyi kararı ile 23. gebelik haftasında gebelik sonlandırıldı. Otopsi incelemesi sol atriyum izomerizmi heterotaksi sendromu ve MKS tanısını doğruladı. Meckel-Gruber sendromlu fetüslerde daha önce birtakım kardiyak defektler bildirilmiş ise de, biz burada sol atriyum izomerizmi ve heterotaksi sendromunu da içeren MKS ile ilişkili kardiyak anomaliler spektrumunu genişletmiş olduk., We aimed to present a fetus with Meckel-Gruber syndrome (MKS) who had left atrial isomerism, heterotaxy syndrome and complete heart block. A 26-year-old healthy female was referred to our clinic in the 23rd week of her preg- nancy. the fetus had multiple systemic anomalies including fetal heart. Fetal echocardiography revealed a horizontal liv- er, left-sided stomach and vena cava interruption with azygos continuation. There was also an apical trabecular ventricular septal defect, aorta and pulmonary artery arising from the left ventricle, pulmonary artery hypoplasia, pulmonary valve stenosis and left atrial isomerism. the heart rate was 46/min, consistent with third-degree atrioventricular block. Multiple anomalies including occipital encephalocele, bilateral poly- cystic kidneys, cleft lip, cleft palate, and polydactyly were also detected in the obstetric ultrasonography. the pregnan- cy was terminated in the 23rd gestational week based on the consensus of perinatology council. the autopsy examination confirmed the diagnosis of MKS, left atrial isomerism and heterotaxy syndrome. Although some cardiac defects have been reported previously in MKS fetuses, here we expand the cardiac spectrum of anomalies associated with MKS to include left atrial isomerism and heterotaxy syndrome.

Objective. The aim of this study is to contribute to the understanding of schizophrenia genetics by using efficient algorithmic examination techniques including dysmorphic examination, karyotyping, and Fluoresence in situ hybridization (FISH). Methods. In this study we have investigated 20 familial schizophrenia patients from Turkey who had an affected first-degree relative. Dysmorphic examination of the schizophrenia cases and their relatives have been performed. High resolution banding (HRB), specific centromeric, subtelomeric and 22q11.2 region FISH probes were used for genotyping of patients. Results. Dysmorphic examination revealed ear, palate, nose, columella anomalies, and obesity in contributing patients, and the pale skin was noticed. The medical histories and clinical findings of two schizophrenia twins were almost identical. HRB study demonstrated the presence of 46,XX[55]/47,XXX[4]/48,XXXX[1] constitution in a paranoid schizophrenia case and 46,XX[67]/45,X[5] karyotype in her mother. FISH studies aiming subtelomeric chromosomal regions revealed no rearrangements and 22q11.2 regions were intact in all of the patients. Conclusions. The parental gonadal mosaicism lying at the origin of the mitotic aneuploidy may be the reason for mosaic X chromosome aneuploidies in our mother-daughter schizophrenia couple. Mosaic X chromosome aneuploidies may accompany schizophrenia cases and may contribute to pathogenesis of familial schizophrenia.

Obesity is a multifactorial disease that is influenced by genetic and environmental factors. The apolipoprotein E (Apo E) polymorphism has been reported to influence some lipid profile abnormalities associated with obesity in childhood. In this study, the relationship between the Apo E gene and Taq1A polymorphisms with childhood obesity has been studied. Regarding the Apo E genotypes, e3/4 was the most frequent in both the patient and control groups. Further, there was a significance between the Apo E genotypes with low density lipoprotein and total cholesterol levels. However, no relationship was found between the Taq1A polymorphism and obesity. In conclusion, polygenic inheritance should be kept in mind when dealing with childhood obesity.

We report a rare case of mosaic ring chromosome 22 duplication/deletion in a fetus for whom karyotype analysis was required because of an abnormal finding in the maternal serum screening test and a choroid plexus cyst detected on prenatal ultrasound. Additional prenatal study of the amniotic fluid by fluorescence in situ hybridization was performed and the terminal 22q13.3 deletion was detected on ring chromosome. The final karyotype was 45,XX,-2[3] / 46,XX,r(22)(p11q13.2)[63] / 46,XX,idicr(22)(p11q13.2;p11q13.2)[2]dn.ishder(22)(N25+, ARSA-, ter-). The pegnancy was terminated. Cytogenetic analysis of the intracardiac blood also revealed ring 22 mosaicism with only one metaphase spread with idicr(22) as the unstable isodicentric rings are subsequently lost from most cells. We discuss the prenatal diagnosis of this rare condition.

Supernumerary marker chromosome 15 (sSMC[ 15]) is the most frequent marker chromosome, and it is generally regarded as unimportant if it does not contain the Prader-Willi/Angelman syndrome critical region (PWACR). The clinical importance of the larger markers in association with the critical region is mentioned in almost all reports related to marker chromosome 15, and smaller markers are solely associated with minor dysmorphic features, azoospermia and recurrent miscarriages. However, these small sSMC(15)s without the PWACR may also determine a specific phenotype. A dysmorphic examination of an azoospermic patient in a genetics clinic was performed and was followed by a peripheral blood lymphocyte chromosomal analysis according to standard cytogenetic methods. Nucleolar region (NOR) banding, C-banding, fluorescence in situ hybridization and a molecular investigation of Y-microdeletions were also performed. The clinical evaluation identified dysmorphic features accompanied with azoospermia and severe 'Angle Class II, Division 1 Open Bite Deformity'. The molecular cytogenetic study revealed the small sSMC(15). In addition, a Y-microdeletion analysis showed that the azoospermia was not the result of a deletion. Although the presented case might represent a coincidental example of supernumerary marker 15 and mandibular anomaly association, the condition may also define a specific phenotype that may be more than azoospermia. This condition may be characterized by infertility, malar hypoplasia, mandibular anomaly, keloid formation and minor dysmorphic features.

Reported here is a 2-year-old girl who was diagnosed to have thiamine-responsive megaloblastic anemia during evaluations for her bilateral neurosensorial deafness. Besides reporting a new mutation on the gene SLC19A2 for the first time in the literature, we highlight the recognition of this syndrome--when megaloblastic anemia and diabetes mellitus coexists--and the role of thiamine replacement for the treatment of both disorders.

Ring chromosome 22, a rare cytogenetic finding, was first described in 1968, and since then about 60 patients have been reported. We describe a new patient with ring chromosome 22 syndrome and discuss the common features of the previously reported cases. Our patient had the major features of this syndrome including mental retardation, hypotonia, motor delay, microcephaly, dysplastic large ears, lack of speech, and hyperactivity disorder. Magnetic resonance imaging findings also revealed an arachnoid cyst, found in the posterior cerebellum. In patients with ring chromosome 22, variable clinical manifestations may be seen due to the size of lost sequences near the telomere. By fluorescent in situ hybridization (FISH) technique, LSI DiGeorge/VCFS/ ARSA locus-specific probes are used to detect deleted sequences. We found that 22q11.2 regions were intact on both chromosomes 22, but 22q13.3 (Arylsulfatase A; ARSA region) was absent in the ring chromosome. As far as we know this is the first reported Turkish patient in the literature.

Major neurological disorders may accompany rare chromosomal abnormalities. As an example of this rare condition, we present a case with microcephaly, mental retardation, developmental delay, hyperactivity, stereotypic movements, seizures and dysmorphic facial appearance in whom a mosaic ring chromosome 18 was found [45,XX,-18/46,XX,r(18)/46,XX,dicr(18)]. Although ring chromosome 18 phenotype has been known for a long time, this is the third reported patient with a dicentric ring chromosome 18 mosaicism. The presented case will contribute to the identification of the genotype-phenotype correlation in chromosome 18 anomalies.