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Background: Idiopathic generalized epilepsy is the most common group of epilepsy disorders in children and adolescents. Various types of genetic abnormality were identified among the hereditary factors that explain epilepsy. Aims: To determine the variations in the etiopathogenesis, treatment protocol planning, and prognosis of idiopathic generalized epilepsy using the next-generation sequencing method. Study Design: A cross-sectional study. Methods: This study included 32 patients with idiopathic generalized epilepsy. Genomic DNA was obtained from peripheral venous blood samples taken from the patients. A total of 18 genes encoding ion channel subunits that are involved in monogenic disorders and are associated with idiopathic generalized epilepsy were included. The targeted custom next-generation sequencing panel was designed to cover all coding exons and all exon/intron splice site regions of 18 genes. Results: We detected 9 (28%) variations, including 1 likely pathogenic (a variant in the SCN1A gene) and 8 of unknown clinical significance (2 in the CLCN2 genes, GABBR2, SCN1B, SLC2A1, SLC4A10 genes, and 2 in the TBC1D24 gene). Conclusion: Study results should be supported by functional advanced studies, with increased existing knowledge in the relevant variations. [ABSTRACT FROM AUTHOR]

Background: Thyroid cancer is the most common malignancy of endocrine system. Genome Wide Association Studies (GWAS) revealed a number of common variants associated with thyroid cancer risk. In this study, we aimed to investigate the association of these known variants with thyroid cancer risk in a Turkish population living in Trakya region. Methods: The study included 97 cases of differentiated thyroid cancer and 379 healthy controls. Real-Time Polymerase Chain Reaction (RT-PCR) method was used for the genotyping of rs965513, rs944289, rs966423 rs2439302 polymorphisms. Results: There was no statistically significant difference between patients and controls in terms of SNP genotype and allele frequencies. The distribution of cumulative genetic risk scores between patients and controls was also not significantly different. In the multiple logistic regression analysis (MLR), it was observed that the relationship of rs2439302 polymorphism GG genotype with thyroid cancer risk has a trend to be significant ((p = 0.067, 95%CI: 2.947 (0.928- 9.357 )). Conclusion: We suggest that the confirmation of the association of common variants with thyroid cancer in different populations will contribute to make a consensus on global risk alleles. The marginal significance of the association of rs2439302 with thyroid carcinoma risk shown in our study supports the need for functional studies on the role of this polymorphism in thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Objective: Alpha thalassemia is a common type of hemoglobinopathy that occurs as a result of deletions or point mutations in the alpha globin gene cluster. The molecular analysis of alpha thalassemia is challenging due to the presence of genes with high sequence similarities in alpha globin gene clusters and pseudogenes. As well as in all genetic diseases, determining the causative mutation types of alpha thalassemia and their frequencies have critical importance for accurate genetic screening and prevention strategies. Material and Method: In our study, alpha globin copy number variations determined by the Multiplex Ligation-dependent Probe Amplifcation (MLPA) method were examined retrospectively with suspicion of alpha thalassemia in 35 female and 43 male patients tested in the Genetic Diseases Diagnosis Center of the Medical Genetics Department at Trakya University Faculty of Medicine. Results: The most common deletion among our patients was the −α3.7 (35.3%), followed by the -α20.5 (10.3%) deletion. The -αSEA deletion was detected in three patients while 4 out of 78 cases were found to have the -αMED deletion. In three patients, a heterozygous large deletion and in one case HS40 regulatory region deletion were detected. In 14 (18%) of the patients, α globin triplications were detected. The -α4.2 deletion was detected in only one of our patients. Conclusion: Our study is the first to report the presence of eight different alpha globin copy number changes and 13 different alpha globin genotypes in the Trakya region. [ABSTRACT FROM AUTHOR]

Introduction: Aneuploids, copy number variations (CNVs), and single nucleotide variants in specific genes are the main genetic causes of developmental delay (DD) and intellectual disability disorder (IDD). These genetic changes can be detected using chromosome analysis, chromosomal microarray (CMA), and next-generation DNA sequencing techniques. Therefore; In this study, we aimed to investigate the importance of CMA in determining the genomic etiology of unexplained DD and IDD in 123 patients. Method: For 123 patients, chromosome analysis, DNA fragment analysis and microarray were performed. Conventional G-band karyotype analysis from peripheral blood was performed as part of the initial screening tests. FMR1 gene CGG repeat number and methylation analysis were carried out to exclude fragile X syndrome. Results: CMA analysis was performed in 123 unexplained IDD/DD patients with normal karyotypes and fragile X screening, which were evaluated by conventional cytogenetics. Forty-four CNVs were detected in 39 (39/123=31.7%) patients. Twelve CNV variant of unknown significance (VUS) (9.75%) patients and 7 CNV benign (5.69%) patients were reported. In 6 patients, one or more pathogenic CNVs were determined. Therefore, the diagnostic efficiency of CMA was found to be 31.7% (39/123). Conclusion: Today, genetic analysis is still not part of the routine in the evaluation of IDD patients who present to psychiatry clinics. A genetic diagnosis from CMA can eliminate genetic question marks and thus alter the clinical management of patients. Approximately one-third of the positive CMA findings are clinically intervenable. However, the emergence of CNVs as important risk factors for multiple disorders increases the need for individuals with comorbid neurodevelopmental conditions to be the priority where the CMA test is recommended. [ABSTRACT FROM AUTHOR]

Epilepsy is a disease historically associated with evil spirits and mystery. The long history of epilepsy dates back to a 4000-year-old Akkadian tablet found in Mesopotamia; It depicts a person "with his neck turned to the left, his hands and feet tense, his eyes wide open, and foam flowing from his mouth without him realizing it". About a thousand years later, Late Babylonians wrote a diagnostic manual called Sakikku, which included texts describing epilepsy. Documentation on epilepsy also dates back to about B.C. It is also found in Chinese texts dated to 770-221. A group of physicians published the Yellow Emperor's Classic of Internal Medicine, the Huang Di Nei Ching, which outlined generalized seizures. The spiritually based pathophysiology of epilepsy dates back to 3000 BC, when the Hippocratic School in Greece suggested that the brain might be the root cause of epilepsy. It remained largely unchallenged until the 5th century. Aristotle, an important philosopher of the 4th century BC, suggested that epilepsy and sleep arise from similar mechanisms. The Hippocratic idea that epilepsy was a brain disease finally gained traction in Europe from the 17th century onwards and continued throughout the millennium. Samuel Tissot (1728-1797), a prominent Swiss physician, published Traité de l'épilepsie in 1770. John Hughlings Jackson (1835-1911) laid the scientific foundation of epileptology and studied the localization of lesions that could cause seizures. He published the influential text "The Study of Convulsion", which was the culmination of his scientific findings. The current focus of gene therapy strategies for epilepsy is primarily on neuropeptide Y, galanin, etc. It aims to reduce neuronal excitability through overexpression of neuromodulatory peptides, such as, or through genetic modification of astrocytes, for example, to suppress adenosine kinase expression. [ABSTRACT FROM AUTHOR]

Maturity onset diabetes of the young (MODY) is characterized by noninsulin-dependent diabetes diagnosed before the age of 25 years with an autosomal dominant inheritance. Rare mutations in the hepatocyte nuclear factor-1-beta (HNF1B) gene produce a syndrome that resembles MODY. About half of patients diagnosed with MODY type 5 due to HNF1B variants, carry a whole gene deletion, known as 17q12 deletion syndrome. 17q12 deletion syndrome is a rare chromosomal anomaly and is typified by deletion of more than 15 genes, including HNF1B resulting in kidney abnormalities and renal cysts, a diabetes syndrome and neurodevelopmental or neuropsychiatric disorders. A 12-year-old girl was referred after high blood sugar was detected in the hospital where she presented with polyuria and polydipsia, which had persisted for one month. Her serum magnesium (Mg) level was low at 1.5 mg/dL (normal value 1.6-2.6) and glycated hemoglobin was 14% (normal value 3.6-5.8) concurrent with a c-peptide of 1.54 ng/mL (normal value 0.8-4). MODY5 was suspected but the NGS gene panel (ABCC8, BLK, CEL, GCK, HNF1A, HNF1B, HNF4A, INS, KCNJ11, KLF11, NEURODD1, PAX4, PDX1, RFX6, ZFP57, GLIS3, FOXP3, NEUROG3, G6PC2) did not identify any abnormality. During follow-up, her serum Mg remained low (1.2 mg/ dL) together with elevated urinary Mg excretion at 172.5 mg/day. An HNF1B variant was again suspected in a patient with chronic hypomagnesemia with normal basal C peptide level. Abdominal computed tomography and magnetic resonance imaging revealed a 43 mm diameter, cystic lesion in the head of the pancreas, with agenesis of the pancreatic neck, trunk and tail. Genetic testing using a microarray analysis was subsequently performed and a heterozygous deletion at 17q12, including HNF1B, was detected. In case of clinical suspicion of HNF1B variants, further genetic examination using other techniques such as MLPA and CGH array may be required to detect the variant. This is because deletions and duplications may not be detected using next generation screening panel techniques. [ABSTRACT FROM AUTHOR]

Aim: The development of whole-genome screening methodologies for the detection of copy number variations (CNVs), such as array-based comparative genomic hybridization (aCHG), provides a much higher resolution than karyotyping leading to the identification of novel microdeletion and microduplication syndromes often associated with an autism spectrum disease (ASD) phenotype. The aim of the study was to determine CNVs of patients with ASD by using array-based comparative genomic hybridization. Methods: Fifty-three patients diagnosed with ASD between 20.01.2014 and 14.01.2015 were included in the study. Chromosome analysis of the patients was performed from peripheral blood cultures and analysed as normal. All patients were evaluated with P064C1 and P096A2 MLPA probes in terms of 16 mental retardation related syndromes. For aCGH method, SurePrint G3 Human microarrays 8x60K were used with genomic DNA isolated from peripheral blood. Results: According to results of 53 patients who were included in and performed with arrayCGH, 8 (15%) patients had CNVs classified as pathogenic or variant of unknown significance (VOUS) in the study. We detected a pathogenic NRXN1 gene partial CNV deletion (2p16.3) in two patients. Also we identified a 900 kb duplication of 4p15.31 including SLIT2 gene, and a 245 kb duplication of 15q11.2 including PWRN1 gene in one patient. Our other findings are considered to be a variant of unknown significance (VOUS). Conclusion: The results of the study support the literature knowledge, where the copy number variations that cannot be detected with conventional cytogenetics methods in terms of size may happen in patients with ASD. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate the possible relationship between Mediterranean fever (MEFV) gene mutations and messenger ribonucleic acid (mRNA) expressions and to identify the link between phenotype and genotype of pediatric patients with Familial Mediterranean fever (FMF). Patients and methods: Seventy-one pediatric FMF patients who were identified with FMF symptoms and diagnosed with FMF according to Tel Hashomer criteria were included at Trakya University, Faculty of Medicine, Department of Paediatric Nephrology. The control group consisted of 73 healthy pediatric participants. Genomic deoxyribonucleic acid was isolated from whole blood samples and the following mutations of MFEV gene were analyzed: E148Q, P369S, H478Y, H479L, S675N, G678E, M680L, M680I (G>A and G>C), T681I, I692del, M694V, M694L, M694I, M695R, M695M, R717S, I720M, V722M, V726A, A744S and R761H. Total RNA isolation from leukocytes was performed and MEFV mRNA expression levels of the patients were compared by using real-time quantitative polymerase chain reaction method. β2 microglobulin was selected as the control gene. The comparison of mRNA expression levels among the patients was performed using the ΔCT method. Results: The most common clinical findings were abdominal pain, fever and vomiting. The mutation detection rate in the patient group was OR=4.1 (95% CI: 1.8-9.0) times higher than that of the control group. The MEFV mRNA expression level of the patients with MEFV gene mutations was lower compared to the control group, indicating statistical significance. Conclusion: Our study results support the findings of previous studies indicating that the MEFV mRNA expression levels of pediatric FMF patients with MEFV gene mutation are lower than the MEFV mRNA expression levels of healthy controls. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate the possible relationship between Mediterranean fever (MEFV) gene mutations and messenger ribonucleic acid (mRNA) expressions and to identify the link between phenotype and genotype of pediatric patients with Familial Mediterranean fever (FMF). Patients and methods: Seventy-one pediatric FMF patients who were identified with FMF symptoms and diagnosed with FMF according to Tel Hashomer criteria were included at Trakya University, Faculty of Medicine, Department of Paediatric Nephrology. The control group consisted of 73 healthy pediatric participants. Genomic deoxyribonucleic acid was isolated from whole blood samples and the following mutations of MFEV gene were analyzed: E148Q, P369S, H478Y, H479L, S675N, G678E, M680L, M680I (G>A and G>C), T681I, I692del, M694V, M694L, M694I, M695R, M695M, R717S, I720M, V722M, V726A, A744S and R761H. Total RNA isolation from leukocytes was performed and MEFV mRNA expression levels of the patients were compared by using real-time quantitative polymerase chain reaction method. β2 microglobulin was selected as the control gene. The comparison of mRNA expression levels among the patients was performed using the ΔCT method. Results: The most common clinical findings were abdominal pain, fever and vomiting. The mutation detection rate in the patient group was OR=4.1 (95% CI: 1.8-9.0) times higher than that of the control group. The MEFV mRNA expression level of the patients with MEFV gene mutations was lower compared to the control group, indicating statistical significance. Conclusion: Our study results support the findings of previous studies indicating that the MEFV mRNA expression levels of pediatric FMF patients with MEFV gene mutation are lower than the MEFV mRNA expression levels of healthy controls. [ABSTRACT FROM AUTHOR]

Objectives: Male infertility is a large and unexplored global health problem in terms of prevalence. Chromosomal polymorphisms may be associated with infertility and recurrent spontaneous abortions. Nonprotein coding and frequently repetitive satellite DNA sequences are found in these regions. Methods: This study aims to present a genetic laboratory experience in the evaluation of frequency, type and significance of Y chromosome polymorphism of Turkish patients with reproductive system problems. The study included 435 patients aged 18-60 years with a documented clinical diagnosis of infertility. Results: In our study, 435 individuals were analyzed cytogenetically and 75 of them (17.24%) were found to carry chromosomally polymorphic variants in Y chromosome. We detected increased heterochromatin structure in the long arm of chromosome Y (Yqh+) as a common variant in our patient group. The frequency of chromosomal polymorphism Yqh-is % 11.26. The rate of chromosomal polymorphism we detected is close to those reported in the literature (10-15%) and statistically significant (p < 0.001), twice that found in the normal population (2-5%). Conclusions: Findings support that Y chromosome polymorphisms may be associated with infertility risk and may play an important role in the development of infertility. More research combining genome studies and other fields is needed to clarify the relationship of Y chromosome polymorphisms with and to infertility. [ABSTRACT FROM AUTHOR]

Objective: To investigate possible mitochondrial DNA (mtDNA) mutations in patients with Leber's hereditary optic neuropathy (LHON) in order to provide a precise diagnosis and genetic counseling. Material and Methods: Between 1982 and 2007, ten patients were clinically diagnosed with LHON and six of these patients agreed to be involved in this study. Six healthy individuals were also included as a control group. mtDNA was isolated from peripheral blood samples and polymerase chain reaction and mtDNA sequence analysis were performed. Results: In one of the six patients, a homoplasmic mutant m.11778G>A mutation was detected. All of the clinically diagnosed LHON patients and the control groups had the m.14212C>T and m.14580G>A single nucleotide polymorphisms (SNPs). The m.11719A>G SNP was detected in three of six patients and four of the controls. Two of the six patients had the m.3197T>C SNP and, in addition, the m.14258G>A SNP was found in one of these two patients, while neither of these mutations were present in the control group. Conclusion: The clinical diagnosis of LHON could be supported by molecular genetics only in one patient by the detection of one mutation. The m.3197T>C and m.14258G>A SNPs should be considered as potential mtDNA mutations due to the fact that they were detected in the patient group.These mutations should be investigated further in large case groups for suspected gene loci that could lead to optic neuropathy. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the study is to explore the MEFV gene exon 2 and exon 10 gene region mutations which take place in etiopathogenesis of Familial Mediterranean Fever in the Thrace population with the DNA sequence analysis method and to compare the results with the other studies. Patients and Methods: The study included patients with Familial Mediterranean Fever who have no relative relationship, have the same linguistic characteristic and live in the Thrace region for at least three generations (34 females, 34 males). MEFV gene exon 2 and exon 10 gene regions multiplied with PCR and their nucleotids were determined with the DNA sequence analysis method. Results: G442C, T306C, A414G, C495A, G605A SNPs were found in MEFV gene exon 2 gene region and G2040C, A2080G, G2082A, A2084G, T2177C, G2282A SNPs were found in MEFV gene exon 10 gene region in the Thrace population. Conclusion: The T306C, A414G, C495A, G605 single-nucleotide polymorphisms in MEFV gene exon 2 gene region and the mutations in exon 10 gene region are not compatible in terms of their frequencies with the results of the other studies. [ABSTRACT FROM AUTHOR]

Free radicals can be defined as atoms or molecules containing one or more unpaired electrons in their orbitals. Their formation occurs continuously in the cells as a consequence of both enzymatic and nonenzymatic reactions. It has been estimated that the average person has around 10000-20000 free radicals attacking each body cell each day. Some free radicals are good in that they enable your body to fight inflammation, kill bacteria, and control the tone of smooth muscles, which regulate the working of internal organs and blood vessels. On the other hand increased or uncontrolled free radical activity might combine with other factors to cause some diseases such as neurodegenerative diseases, heart disease, cancers etc. The balance between the production of free radicals and the antioxidant defences in the body has important health implications. Under the normal conditions the antioxidant defense system within the body can easily handle free radicals that are produced. If there are too many free radicals produced and too few antioxidants, this may cause chronic damage. The aim of this study is review the data on diseases which may be linked to free radicals in order to clarify the role of them in ethiopathogenesis of these diseases. [ABSTRACT FROM AUTHOR]

Introduction: Genetic factors play an important role in the etiopathogenesis of autism spectrum disorder (ASD). The Pogo Transposable Element with ZNF Domain protein (POGZ) gene (MIM*614787) has been reported to be one of the most frequently mutated genes associated with ASD. This study aims to analyze the exonic regions of the POGZ gene in individuals diagnosed with non-syndromic ASD. Methods: Fifty-one non-syndromic cases diagnosed with ASD according to the DSM-V diagnostic criteria, aged 2-18 years, were included in the study. The healthy control group consisted of 50 children of similar age groups without neurodevelopmental problems. Amplicons produced using deep intronic primers covering the mRNA-encoded regions of the POGZ gene from at least 50 base pairs were sequenced by Next Generation Sequencing Analysis. Results: No pathogenic or likely pathogenic variants reported in open-access databases (ClinVar, HGMD, etc.) were detected in the case group. In the ASD and healthy control groups, rs113396244, rs11204811, rs779479223, rs772352054, rs3831142, rs112072925, rs227453 and rs142860188 variants were determined. The rs3831142, rs112072925, rs2274535, rs142860188 variants were found statistically significant in the ASD group. The distribution of the cases with detected single nucleotide polymorphisms (SNPs) according to gender was not statistically significant. Conclusion: The variants identified as statistically significant within the patient group are situated in regions that encompass both the HP1-ZNF and DDE domains of the protein. Given the crucial role that the DDE domain plays, particularly in fetal brain development and neurogenesis, these four variants may potentially possess modifying and/or predisposing effects in the context of ASD. [ABSTRACT FROM AUTHOR]

Aim: Mandibulofacial dysostosis type Guion-Almeida was characterized by microcephaly, a characteristic craniofacial appearance with upslanting palpebral fissures, microtia, preauricular and buccal tags and intellectual disability. EFTUD2 gene was found to cause a very distinct condition with phenotypic overlap with Treacher Collins syndrome, the mandibulofacial dysostosis type Guion-Almeida (MFDGA). Methods: G-banding karyotype performed using peripheral blood. TCOF1, POLR1C and POLR1D genes associated with Treacher Collins syndrome were studied by NGS method. Chromosomal microarray analysis was performed on the proband and her parents using Agilent Technologies 4x180K SurePrint G3 Human CGH+SNP Platform. Results: A 5 years old female referred us with Treacher Collins syndrome. She was born at 37th weeks of gestation with CS as weight 3200g. Her parents were nonconsanguineous and healthy. She had a 10 years old healty brother. The patient had speech delay, history of 4-5 seizures, convulsion and hypotonia. She had a dysmorphic features including long philtrum, broad nasal bridge, broad nasal root, bulbous nose, short neck, dysplastic ear, low nape hairline, micrognathia/retrognathia. The echocardiogram revealed as normal, cranial MR revealed arachnoid cysts. Hearing test results were normal. Chromosomal analysis and NGS analysis were evaluated as normal. A 207 kb copy number variation arr[GRCh37]17q21.31(42753313-42960557)×1 was identified in our patient. Her parents arrayCGH analyses revealed as normal. Conclusion: Our array CGH finding was reported extremely rare previously. We anticipate that the findings of our patient are due to deletion of 17q21.31 and loss of function of the EFTUD2 gene. [ABSTRACT FROM AUTHOR]

İnsan boyu, hem genetik hem de çevre faktörlerinin kontrolü altındaki kompleks bir özelliktir. Kısa boy, genel popülasyondaki bireylerin % 2-3'ünü etkilemekte olup sosyal ve tıbbi öneme sahiptir. Genel olarak boyun kalıtılabilirliği % 50'nin üstündedir ve çalışılmış kompleks insan özellikleri arasında kalıtılabilirlik oranı en yüksek olanıdır. 2008 yılında yapılan İBK konsensüs toplantısında (Cohen ve ark., 2008) İBK tanımı şu şekilde kabul edilmiştir: 'İBK bilinen sistemik, endokrin, nutrisyonel ve kromozomal bir hastalık olmadan boyun aynı yaş, cinsiyet ve popülasyon grubu için verilen boy ortalamasının -2 SSD'nin altında olmasıdır'. Geçtiğimiz birkaç yılda BK'nın birçok nedeni keşfedilmiştir ve tüm genom ilişkilendirme çalışmaları sonucunda normal popülasyonda boyda varyasyona neden olan birçok gen bulunmuştur. Bu doğrultuda boy kısalığı tanısıyla Trakya Üniversitesi Tıbbi Genetik Anabilim Dalı'nda değerlendirilen 8 hasta konvansiyonel sitogenetik yöntemle incelendi. Yapılan sitogenetik inceleme sonucunda tüm vakaların karyotipi normal olarak değerlendirildi. Daha sonra bu hastalarda Aquarius SHOX (Catalog No: LPU 025, Cytocell) probu kullanılarak FISH analizi gerçekleştirilmiştir. Prob, SHOX genini tamamen kapsayan yaklaşık 160kb uzunluğunda bir diziyi göstermektedir. Her hasta için 20 metafaz değerlendirilmiştir. Değerlendirme sonuçlarında SHOX bölgesinde herhangi bir değişiklik tespit edilmemiştir. SHOX'un tek doz yetersizliği, insanlarda görülen Turner Sendromu (TS), İdiopatik Kısa Boy (İKB) ve LeriWeill Diskondrosteozu (LWD) olmak üzere üç farklı büyüme hastalığına katkıda bulunmaktadır. SHOX delesyonuna sahip bireyler hafif, zorlukla ortaya konabilen iskelet malformasyonlarından, bu hastaların yaşamlarını olumsuz yönde etkileyen ciddi displazilere kadar değişen hatırı sayılır bir fenotipik heterojenite göstermektedirler. Hastaların son olarak periferik kan örneklerinden elde edilen DNA ile Cytosure 4x180K oligonükleotit problar (Agilent Technologies, Inc.) kullanılarak aCGH yapıldı. aCGH CNV+ SNP değişimlerini araştırmak için yapıldı. Çalışma sonucunda 8 hastadan 2 tanesinde CNV saptanmıştır. 2007 doğumlu kadın hastada 17p13.3 bant bölgesinde 2Mb lık delesyon saptanmıştır. 1985 doğumlu bir diğer kadın hastada ise 1q42 bant bölgesinde TSNAX-DISC1 gen bölgelerini kapsayan 141kb'lık delesyon saptanmıştır. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the molecular basis of maturity-onset diabetes of the young (MODY) by targeted-gene sequencing of 20 genes related to monogenic diabetes, estimate the frequency and describe the clinical characteristics of monogenic diabetes and MODY in the Trakya Region of Turkey. Methods: A panel of 20 monogenic diabetes related genes were screened in 61 cases. Illumina NextSeq550 system was used for sequencing. Pathogenicity of the variants were assessed by bioinformatics prediction software programs and segregation analyses. Results: In 29 (47.5%) cases, 31 pathogenic/likely pathogenic variants in the GCK, ABCC8, KCNJ11, HNF1A, HNF4A genes and in 11 (18%) cases, 14 variants of uncertain significance (VUS) in the GCK, RFX6, CEL, PDX1, KCNJ11, HNF1A, G6PC2, GLIS3 and KLF11 genes were identified. There were six different pathogenic/likely pathogenic variants and six different VUS which were novel. Conclusion: This is the first study including molecular studies of twenty monogenic diabetes genes in Turkish cases in the Trakya Region. The results showed that pathogenic variants in the GCK gene are the leading cause of MODY in our population. A high frequency of novel variants (32.4%-12/37) in the current study, suggests that multiple gene analysis provides accurate genetic diagnosis in MODY. [ABSTRACT FROM AUTHOR]

Objectives: In this study, we aimed to identify patients with systemic lupus erythematosus (SLE) who are genetically at risk for developing atherosclerosis. Patients and methods: Between November 2014 and May 2016, a total of 38 patients with SLE (36 females, 2 males; mean age: 37.6 years; range, 18 to 71 years) and 32 healthy females (mean age: 31.5 years; range, 19 to 54 years) were included in the study. Carotid intima-media thickness (CIMT) was measured using high-resolution B-mode ultrasonography. SurePrint G3 Human Gene Expression 8x60K Microarray kit was used in our study. Genes showing differences in expression between the groups were identified by using GeneSpring GX 10.0 program. Pathway analyses of gene expressions were performed using Ingenuity Pathways Analysis (IPA). Gene ontology analyses were performed using the Protein Analysis Through Evolutionary Relationships (PANTHER). Results: Clinical findings of SLE patients were mainly photosensitivity (71.1%), arthritis (63.2%), lupus nephritis (55.3%), thrombocytopenia (26.3%), and autoimmune hemolytic anemia (21.1%). A total of 155 genes showing expression level difference were detected between SLE patients and healthy controls. In molecular network analysis, 28.2% of all genes were found to be directly or indirectly associated with atherosclerosis and cardiovascular disease. Conclusion: In SLE patients, many genes are expressed differently from healthy individuals. Expression of these genes is important in the pathogenesis of SLE. Genes identified differently in gene expression analysis can help us to identify SLE patients at risk for atherosclerosis in the Turkish population. [ABSTRACT FROM AUTHOR]

Objective: Genetic factors, including Y chromosome microdeletions, are responsible for about 10% of male infertility cases and are particularly associated with azoospermia or severe oligozoospermia. In our study, it was aimed to determine the frequency of Y chromosome microdeletions in the Thrace region and to provide information about the heterogeneous phenotype in infertile male patients with AZF microdeletion. Material and Method: Chromosome analysis and Y chromosome microdeletion analysis were performed on 446 male patients with non-obstructive azoospermia or oligozoospermia, who applied to the Trakya University Hospital Medical Genetics Department Genetic Diseases Diagnosis Center clinic between the years 2011-2019. Results: Y chromosome microdeletion was detected in 19 (4.26%) of 446 cases. Structural chromosomal anomalies were accompanied in 5 of 19 cases with Y chromosome microdeletions. Three hundred fifty-two cases had no Y chromosome microdeletion, 35 (9.94%) of these cases had Klinefelter syndrome, 1 (0.28%) case had Klinefelter syndrome low grade mosaicism, 3 (0.85%) cases had Robertsonian translocation carriage, and 1 (0.28%) had Reciprocal translocation carriage. Conclusion: Y chromosome microdeletion screening in non-obstructive azoospermic or oligosoospermic infertile male patients has prognostic value and affects clinical prognosis. The results of our study support the proposal to perform Y chromosome microdeletion analysis before microTESE in azoospermic or oli gosoospermic infertile male patients as reported in the literature. [ABSTRACT FROM AUTHOR]

• A novel area-based diameter measurement algorithm for industrial machine vision. • Calculating diameter using boundary pixel intensities. • Fast diameter measurement algorithm for machine vision applications. • Robust threshold selection to determine boundary gray level pixels. In recent years, there has been a notable surge in the utilization of industrial image processing applications across various sectors, including automotive, medical, and space industries. These applications rely on specialized camera systems and advanced image processing techniques to accurately measure working products with precise tolerances. This research presents a novel fast algorithm for measuring the diameter of a ring, employing a subpixel counting method. The algorithm classifies image pixels into two categories: full pixels and transition pixels. Full pixels reside entirely within the inner region of the workpiece, while transition pixels represent gray pixels that reside at the boundary between the workpiece and its background. To ensure accurate determination of the object area, the proposed method incorporates normalization to account for the contribution of transition pixels alongside full pixels. Subsequently, the circle area equation is employed to calculate the diameter. Moreover, a robust threshold selection method is introduced to effectively distinguish pixels with gray intensities. The experimental setup consists of an industrial camera equipped with telecentric lenses and appropriate illumination. The results demonstrate that the proposed algorithm achieves a 3–10 % improvement in accuracy compared to existing approaches. In terms of measuring sensitivity, the operational sensitivity of the proposed methodology is quantified as 1/20th of the pixel size, exhibiting an average uncertainty of 1 µm. Furthermore, the proposed method surpasses existing works by at least 12.5 % to 35 % in terms of benchmarking computing time. [ABSTRACT FROM AUTHOR]

An abstract of the article "Investigation of CYP21A2 Gene Variants in Patients Pre-diagnosed with Congenital Adrenal Hyperplasia," by Hakan Gürkan and colleagues is presented.

An abstract of the article "Application of Next-Generation Sequencing Technology for CFTR Mutation Screening," by Selma Ulusal and colleagues is presented.

Objectives: Investigation of CYP21A2 gene variants in patients pre-diagnosed with congenital adrenal hyperplasia (CAH) (premature pubarche, virilization). Methods: Two milliliters of peripheral blood samples were collected from the patients. Genomic DNA isolation from nucleated cells of the peripheral blood was performed according to the manufacturer's protocol (EZ1 Advanced Instruments, Qiagen, Hilden, Germany). Exons and exonintron boundaries of CYP21A2 gene were amplified according to the protocol of the kit (GML AG, Wollerau/Switzerland). Band patterns of amplicons were checked by agarose gel electrophoresis. Nucleotide sequences of the amplicons were defined by Sanger sequencing method (ABI 3130 Avant system, Applied Biosystems, Grand Island, NY 14072, USA). Analysis of the results was performed using SeqScape v2.7 programme (Transcript: CYP21A2-002 ENST00000418967). Results: Four female patients were included in the study. Mean age of the patients was ±9.75. c.-4C>T [5'UTR, rs6470], c.308G>A [p.Arg103Lys, rs6474], c.806G>C [p.Ser269Thr, rs6472, HGMD: CM994664], c.1360C>T [p.Pro454Ser, rs6445], c.1473G>A [p.Pro491=, rs6446], c.1481G>A [p.Ser494Asn, rs6473], c.293-13C>A [IVS2AS, rs6467, HGMD: CS880069], c.*52C>T [3'UTR, rs1058152] variations were defined during the analysis of CYP21A2 sequences. Conclusion: The results were assessed considering the International genetic databases "dbSNP" and "The Human Gene Mutation Database (HGMD)". rs6470, rs6474, rs6446, and rs1058152 variations of the patients were reported as "polymorphism" in the dbSNP and HGMD. rs6467 (HGMD: CS880069), rs6472 (HGMD: CM994664), and rs6473 variations have been associated with CAH (21-hydroxylase deficiency) and rs6445 variation has been associated with CAH (21-hydroxylase deficiency) non-classical type. We found the following variations of the CYP21A2 gene: rs6473 - in our first patient followed up for premature pubarche, rs6445 and 6473 - in our second patient followed up for virilization, rs6467 and rs6472 - in the third patient, and rs6473 and rs6472 - in the fourth patient. The CYP21A2 gene variations determined in the patients supported the clinical pre-diagnosis. [ABSTRACT FROM AUTHOR]

Objective: We report here the results of next-generation sequencing analysis of CFTR gene in first ten patients. Methods: Genomic DNA was isolated from blood samples of ten patients who had been referred to our center for CFTR gene mutation screening for different indications. AmpliSeq libraries were produced by using Ion Ampliseq Library Kit for coding regions (NT_007933.16) of the CFTR gene (NG_016465.3). Amplicons were enriched by using Ion PGM Template OT2 200 Kit and sequenced on Ion Torrent Personal Genome Machine by using Ion PGM Sequencing 200 Kit v2. hg19 (Genome Reference Consortium GRCh37) was used as a reference. Torrent Suite Software v4.2, VariantCaller (v4.2-r88446) and Ion Reporter Software 4.2 were used for the analysis. IGV_2.3.8 was used to visualize the sequences. Mutations were confirmed using the Sanger sequencing method. Results: There was no pathogenic mutation in five out of ten cases. There was one patient each for the following mutations: homozygous c.1521_1523delCTT, heterozygous c.1521_1523delCTT, c.3154T>G (p.Phe1052Val), and heterozygous c.3683A>G (E1228G). There was a heterozygous c.1576C>G (L526V) mutation in a patient directed to us for CFTR mutation screening before conception. Conclusion: The patient that we found to have a homozygous c.1521_1523delCTT mutation has being followed-up for cystic fibrosis. c.1576C>G (L526V) mutation that we found in the other patient was not reported in the literature before. This mutation was tested in Mutation Taster and Polyphen and it was concluded that it may have a pathogenic affect. As a result, we suggest that nextgeneration sequencing method can be used as a successful method to screen CFTR gene mutations. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed at evaluating and improving the knowledge regarding prenatal test indications by assessing the results of the invasive prenatal tests for the detection of fetal chromosomal anomalies conducted in our tertiary center. Material and Methods: A retrospective study was conducted to collect the results of prenatal invasive procedures performed in our tertiary center between January 2002-September 2017. The types and prevalence of fetal chromosomal anomalies were identified and the efficiency of the invasive procedure indications in predicting these fetal chromosomal anomalies was investigated. Results: The results of 2136 invasive procedures (2014 amniocentesis, 80 cordocentesis, and 42 chorion villus samplings) revealed 101 (4.72%) fetal chromosomal anomalies and 128 (5.99%) chromosomal polymorphisms. The most common chromosomal anomaly observed was trisomy 21 (n=52), followed by trisomy 18 (n=12). In terms of diagnosis of the fetal chromosomal anomalies, the following observations were made: the indication "major structural anomaly in the ultrasound (USG)" exhibited 31.68% sensitivity and 82.03% specificity with an odds ratio (OR) of 2.11 (95% CI: 1.37-3.27); the indication "screening test positivity" exhibited 44.55% sensitivity and 48.25% specificity [OR=0.75 (95% CI: 0.50-1.13)]; and the co-existence of "major structural anomaly in the USG" and "screening test positivity" exhibited 8.91% sensitivity and 98.24% specificity [OR=5.49 (95% CI: 2.54-11.84)]. Conclusion: Fetal chromosomal anomaly rate was observed to be 4.72%. The co-existence of a sonographic major fetal structural anomaly and serum screening test positivity was observed to maximize the risk of numerical as well as a structural chromosomal anomaly. The data from the present study which reflected screening performances of detailed USG and biochemical screening tests for the detection of fetal chromosomal anomalies may be useful for clinicians while performing detailed counseling of patients. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis is the most common chronic inflammatory skin disease. A complex interaction of both genetic and environmental factors is thought to contribute to the disease. Aims: To evaluate whether single nucleotide polymorphisms in the TLR2 gene c.2258C>T (R753Q) (rs5743708) and TLR2 c.-148+1614T>A (A-16934T) (rs4696480) (NM_0032643) are associated with atopic dermatitis in Turkish children. Study Design: Case-control study. Methods: The study was conducted on 70 Turkish children with atopic dermatitis aged 0.5-18 years. The clinical severity of atopic dermatitis was evaluated by the severity scoring of atopic dermatitis index. Serum total IgE levels, specific IgE antibodies to inhalant and food allergens were measured in both atopic dermatitis patients and controls, skin prick tests were done on 70 children with atopic dermatitis. Genotyping for TLR2 (R753Q and A-16934T) single nucleotide polymorphisms was performed in both atopic dermatitis patients and controls. Results: Cytosine-cytosine and cytosin-thymine genotype frequencies of the TLR2 R753Q single nucleotide polymorphism in the atopic dermatitis group were determined as being 98.6% and 1.4%, cytosine allele frequency for TLR2 R753Q single nucleotide polymorphism was determined as 99.29% and the thymine allele frequency was 0.71%, thymine-thymine, thymine-adenine, and adenine-adenine genotype frequencies of the TLR2 A-16934T single nucleotide polymorphism were 24.3%, 44.3%, and 31.4%. The thymine allele frequency for the TLR2 A-16934T single nucleotide polymorphism in the atopic dermatitis group was 46.43%, and the adenine allele frequency was 53.57%, respectively. There was not statistically significant difference between the groups for all investigated polymorphisms (p>0.05). For all single nucleotide polymorphisms studied, allelic distribution was analogous among atopic dermatitis patients and controls, and no significant statistical difference was observed. No homozygous carriers of the TLR2 R753Q single nucleotide polymorphism were found in the atopic dermatitis and control groups. Conclusion: The TLR2 (R753Q and A-16934T) single nucleotide polymorphisms are not associated with atopic dermatitis in a group of Turkish patients. [ABSTRACT FROM AUTHOR]

Objective: In a multiethnic community, our goal was to assess the applicability of this method. Here we offer a collection of 112 diagnostic prenatal samples for which a comprehensive study of exons, exons/intron boundaries, and major rearrangements has been investigated in prenatal samples of fetuses with suspected cystic fibrosis over the past decade. Methods: For the CFTR mutation study, 112 prenatal samples (amniotic fluid, chorionic villi, or cultured cells from amniotic fluid or chorionic villi) were brought into our lab. QIAseq Targeted NGS DNA Panel (Qiagen, Hilden, Germany) was performed to analyze the CFTR gene (27 exons). Results: The pathogenic variation NM000492.4(CFTR):c.3454G>C was the most often found (p.Asp1152His), which accounted for 50% of the classic pathogenic CF variants in the study population. Compound heterozygous CFTR pathogenic variations were detected in one of our patients. NM000492.3(CFTR):c.2620-15C>G and NM000492.3(CFTR):c.2756A>G Two variants, one of which was reported as VUS and the other as pathogenic, were detected in a 17-week - old fetus (0.89%). Fetus inherited the NM000492.3(CFTR):c.2756A>G variant from mother and the NM000492.3(CFTR):c.2620-15C>G variant from father. There is an isolated hyperechoic bowel sign at 17 weeks of pregnancy. Conclusion: In our case series, genetic analyzes suggest that an affected child may be heterozygous for CFTR mutations, compound heterozygous for two clinically significant recessive mutations inherited from healthy carrier parents. Early prenatal genetic testing pretesting and posttesting genetic counseling is crucial in the management of future pregnancies in heterozygous couples which are healthy carriers for CFTR mutations. [ABSTRACT FROM AUTHOR]

Introduction: X-linked hypophosphatemic is a result of a mutation which leads to loss of function in the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene. The case is here presented of a patient followed up for XLH rickets, with the formation of a stop code through frame-shifting mutation in the PHEX gene. Case Report: An 18-month old male infant presented at our clinic with the complaint of curvature in the legs. In the physical examination of the infant, height was measured as 78 cm (-1.67 SDS) and weight was 12.5 kg (0.52 SDS). Deformity was present in the frontal protusion, the wrist widths and the legs. Laboratory test results were determined as phosphorus: 2.3 mg/dL (n=3.5-4.7), calcium: 9.8 mg/ dL (n=8.5-10.5), alkaline phosphatase (ALP) 707 IU/L (n=40-150), 25(OH) D vitamin:18 μg/L (n=18-40), PTH: 79 pg/mL (n=15-68), and tubular phosphorus reabsorption was low (71%). Visualisation on wrist radiographs of collapse in the metaphyseal sections of the radus and ulna and metaphyseal irregularity. Conventional treatment was started. Next generation sequence analysis of the proband revealed the presence of a hemizygous c.281&lowbar;288delTTCCCGAA (p.lle94ArgfsTER14) frameshift variant in PHEX gene. This novel variant is pathogenic according to the ACMG criteria, and not reported in any database before. While full-fill clinical recovery was not achieved with conventional treatment and some complications occured, Burosumab treatment was started. Conclusion: Here presented of a patient who was diagnosed with XLH, and was then determined with a novel mutation in the PHEX gene. The current treatment options directed at the basic pathology render genetic diagnosis more important in cases of hypophosphatemic rickets. [ABSTRACT FROM AUTHOR]

Objective: In a multiethnic community, our goal was to assess the applicability of this method. Here we offer a collection of 112 diagnostic prenatal samples for which a comprehensive study of exons, exons/intron boundaries, and major rearrangements has been investigated in prenatal samples of fetuses with suspected cystic fibrosis over the past decade. Methods: For the CFTR mutation study, 112 prenatal samples (amniotic fluid, chorionic villi, or cultured cells from amniotic fluid or chorionic villi) were brought into our lab. QIAseq Targeted NGS DNA Panel (Qiagen, Hilden, Germany) was performed to analyze the CFTR gene (27 exons). Results: The pathogenic variation NM000492.4(CFTR):c.3454G>C was the most often found (p.Asp1152His), which accounted for 50% of the classic pathogenic CF variants in the study population. Compound heterozygous CFTR pathogenic variations were detected in one of our patients. NM000492.3(CFTR):c.2620-15C>G and NM000492.3(CFTR):c.2756A>G Two variants, one of which was reported as VUS and the other as pathogenic, were detected in a 17-week - old fetus (0.89%). Fetus inherited the NM000492.3(CFTR):c.2756A>G variant from mother and the NM000492.3(CFTR):c.2620-15C>G variant from father. There is an isolated hyperechoic bowel sign at 17 weeks of pregnancy. Conclusion: In our case series, genetic analyzes suggest that an affected child may be heterozygous for CFTR mutations, compound heterozygous for two clinically significant recessive mutations inherited from healthy carrier parents. Early prenatal genetic testing pretesting and posttesting genetic counseling is crucial in the management of future pregnancies in heterozygous couples which are healthy carriers for CFTR mutations. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the production of autoantibodies and the involvement of multiple organ systems. Systemic sclerosis (SSc) is another autoimmune disease that causes fibrosis. We will aim to analyse the role of killer cell immunoglobulin-like receptor (KIR) genotypes and their existence with the respective HLA ligands in patients with SLE and SSc. Forty-five SLE, 25 SSc and 40 healthy controls were included. We examined the presence/absence of KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5A, 2DL5B, 2DS1, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1, 2DP1, 3DP1 and their known HLA ligands. In the SLE group, the KIR2DL5, KIR2DL5B and KIR2DS3 genes were significantly more frequent, and KIR2DL3 gene was significantly less than in controls ( p values <0.05). In SSc patients, the KIR2DS3 gene was more frequent than in controls (p = 0.032). The KIR2DL3 gene was detected more frequently in controls while KIR2DS3 gene was more frequent in the patient group when SLE and SSc patients were combined ( p values < 0.05). The KIR2DS2/HLA-C and KIR2DS2/HLA-C combinations were significantly more in both SLE and SSc groups than in controls. The KIR2DL2 and KIR2DL5B genes were protective from neurologic involvement in SLE patients ( p values <0.05). The variations of some KIR genes such as KIR2DL5, KIR2DL5B, KIR2DS3 and KIR2DL3 may have a role in the pathogenesis of SLE and SSc. Also, the presence of KIR2DL2 and KIR2DL5B may cause major organ involvement, like neurologic involvement, in SLE. [ABSTRACT FROM AUTHOR]

Acute promyelocytic leukemia (APL) differs from other forms of acute myeloid leukemia (AML), including coagulopathy, hemorrhage, disseminated intravascular coagulation (DIC), and treatment success with all-trans retinoic acid (ATRA). Despite ATRA, early deaths (ED) are still common in APL. Here, we evaluated factors associated with ED and applicability of scoring systems used to diagnose DIC. Ninety-one APL patients (55 females, 36 males, and median age 40 years) were included. ED was defined as deaths attributable to any cause between day of diagnosis and following 30th day. DIC was assessed based on DIC scoring system released by the International Society of Thrombosis and Hemostasis (ISTH) and Chinese Diagnostic Scoring System (CDSS). Patients' median follow-up time was 49.2 months, and ED developed in 14 (15.4% of) cases. Patients succumbing to ED had higher levels of the Eastern Cooperative Oncology Group Performance Status (ECOG PS), lactate dehydrogenase (LDH), and ISTH DIC, and lower fibrinogen levels (p <0.05). In multivariate Cox regression analysis, age >55 and ECOG PS ≥2 rates were revealed to be associated with ED. Based on ISTH and CDSS scores, DIC was reported in 47.3 and 58.2% of the patients, respectively. Despite advances in APL, ED is still a major obstacle. Besides the prompt recognition and correction of coagulopathy, those at high ED risk are recommended to be detected rapidly. Implementation of local treatment plans and creating awareness should be achieved in hematological centers. Common utilization of ATRA and arsenic trioxide (ATO) may be beneficial to overcome ED and coagulopathy in APL patients. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, the new method of speech modeling which is called SYMPES (A Novel Systematic Procedure to Model Speech Signals via Predefined “Envelope and Signature Sequences”) is introduced and it is compared with the commercially available methods. It is shown that for the same compression ratio or better, SYMPES yields considerably better hearing quality over the coders such as G.726 (ADPCM) at 16kbps and voice-excited LPC-10E of 2.4kbps. [Copyright &y& Elsevier]

Background: Tuberous Sclerosis Complex is an autosomal dominant multi-system disorder with an incidence of about 1 in 6000 live births. Defects in either TSC1 (* 605284) or TSC2 (* 191092) genes encoding the components of the Tuberous Sclerosis Complex are responsible for the disease. Therefore, consideration of TSC1/TSC2 pathogenic variations is recommended in the updated diagnostic criteria of Tuberous Sclerosis Complex. Aims: To present the TSC1/TSC2 screening results of a mixed patient population as well as possible new variants in 23 cases from 20 different families who were referred to our Genetic Diseases Diagnosis Center with the signs and symptoms of Tuberous Sclerosis Complex. Study design: Retrospective, cross-sectional study. Methods: Germline TSC1/TSC2 variants were screened in DNA samples extracted from peripheral blood samples of 23 patients from 20 unrelated families using targeted high-throughput sequencing and multiplex ligation-dependent probe amplification methods. The variants identified were classified according to ACMG 2015 guidelines. Results: In total, 5 different pathogenic/likely pathogenic changes have been defined. All these pathogenic/likely pathogenic variants were located in the TSC2 gene. Three of the pathogenic/likely pathogenic variants were novel. Two patients who are twin sisters were found to have TSC2/PKD1 contiguous deletion syndrome. One of the 3 novel variants was a mosaic in-frame deletion. We did not identify any pathogenic variants of the TSC1 gene. Conclusion: The novelty of most of the variants found, including a mosaic likely pathogenic variant, and the presence of a large genomic rearrangement, supports the importance of a comprehensive approach in analyzing TSC1/TSC2 genes. Genetic diagnosis should be performed with caution, considering the possibility of mosaic variants with low allelic fractions. [ABSTRACT FROM AUTHOR]

Objective: Osteogenesis imperfecta (OI) includes a group of disorders characterized by susceptibility to bone fractures with different severities. The increasing number of genes that may underlie the disorder, along with the broad phenotypic spectrum that overlaps with other skeletal diseases, provided a compelling case for the use of high-throughput sequencing (HTS) technology as an aid to OI diagnoses. The aim of this analysis was to present the data from our 5-year targeted HTS results, that includes the reporting of 9 novel and 24 known mutations, found in OI patients, from 5 different regions of Turkey. Materials and Methods: We performed a retrospective cross-sectional study, reporting the HTS results of 43 patients (23 female and 20 male; mean age: 9.5 years), directed to our center with a suspicion of OI between February 2015 and May 2020. Genetic analyses were also performed for 24 asymptomatic parents to aid the segregation analyses. We utilized an HTS panel targeting the coding regions of 57 genes associated with a reduction, increase, or abnormal development of bone mineralization. In addition, we sequenced the entire coding region of the IFITM5 gene through HTS. Results: Thirty-nine patients had at least one pathogenic/likely pathogenic variation (90.69%) in the COL1A1 (56.41%), COL1A2 (20.51%), FKBP10 (7.7%), P3H1 (5.13%), IFITM5 (5.13%), CTRAP (2.56%), or TMEM38B (2.56%) genes. Nine of the determined pathogenic/likely pathogenic variations were novel. The recurrent pathogenic mutations were c.1081C>T (p.Arg361Ter) (3/43), c.1405C>T (p.Arg469Ter) (2/43), and c.3749del (p.Gly1250AlafsTer81) in COL1A1 gene, along with c.-14C>T variation in the 5'UTR of the IFITM5 gene (2/43) and the c.890_897dup variation in the FKBP10 gene (2/43). Three out of 43 patients were carrying at least one additional variant of unknown significance, highlighting the importance of a multigene panel approach and segregation analyses. Conclusion: We suggest that a targeted HTS panel is a feasible tool for genetic diagnosis of OI in patients. [ABSTRACT FROM AUTHOR]

Aims: Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder characterized by telangiectasia, epistaxis, and vascular malformations. Pathogenic mutations were found in ENG, AVCRL1, SMAD4, and GDF genes. In this study, we present our database of patients with hereditary hemorrhagic telangiectasia regarding the phenotype-genotype relations and discuss two novel ENG gene pathogenic variations in two unrelated families. Methods: Next Generation Sequencing analysis was performed on the peripheral blood of nine patients with hereditary hemorrhagic telangiectasia in four unrelated families. All patients were diagnosed with hereditary hemorrhagic telangiectasia according to the Curaçao criteria. Data on treatment and screenings of visceral involvement were recorded from files. Results: We have found a pathogenic variation in either the ENG or ACVRL1 gene in each family. Two novel pathogenic variations in the ENG gene, including NM&lowbar;000118.3 (ENG): c.416delC (p.P139fs*24) and NM&lowbar;000118.3(ENG): c.1139dupT (p.Leu380PhefsTer16), were found in the same family. The NM&lowbar;000020.2(ACVRL1): c.1298C>T (p.Pro433Leu) pathogenic variation in the ACVRL1 gene in our first family and a novel heterozygous likely pathogenic NM&lowbar;000020.2(ACVRL1): c.95T>C (p.Val32Ala) variation was found in our second family. Seven of the nine patients were treated with thalidomide for controlling bleeding episodes. All patients responded to thalidomide. In one patient, the response to thalidomide was lost and switched to bevacizumab. Conclusion: In hereditary hemorrhagic telangiectasia, certain types of mutations correlate with disease phenotypes and with next generation sequencing methods. New pathogenic variations can be revealed, which might help manage patients with hereditary hemorrhagic telangiectasia. [ABSTRACT FROM AUTHOR]

Introduction: Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors. Clinical manifestations consist of various cardiovascular signs and symptoms related to excessive secretion of catecholamines. Catecholamine-induced cardiomyopathy is a rare but life-threatening complication of PPGL. Excessive discharge of catecholamines results in vasoconstriction, coronary vasospasm and myocardial ischemia. Three types of cardiomyopathies can be observed in patients with PPGL; dilated cardiomyopathy, Takotsuba cardiomyopathy and hypertrophic cardiomyopathy. Clinical Case: Herein, we present a case with PPGL complicated with heart failure probably due to excessive secretion of catecholamines. A 19 years-old man was admitted to emergency department with dyspnea and hypotension. He exhibited severe signs of heart failure with very high liver function tests; ALT: 3647 U/L (8-65) and AST: 4542U/L (7-40), probably due to hepatic congestion. Echocardiogram performed in ICU reported %10 left venticular ejection fraction with diffuse akinesia. Remarkable improvement of liver function was recorded following the introduction of heart failure medicines. A computed tomography scan that was performed for abdominal pain and distension revealed a six cm tumour at the left adrenal gland compatible with pheochromocytoma. Laboratory analyses were; 24-hour urine metanephrines: 1938mcg (44-261), normetanephrines: 17934mcg (103-390). Following necessary preoperative preparations, laparoscopic left adrenalectomy was performed and a 70 mm adrenal tumor, histopathologically compatible with pheochromocytoma, was excised. His postoperative laboratory findings were; 24-hour urine metanephrines: 248 mcg (44-261), normetanephrines: 4368 mcg (103-390), chromogranin A: 554.9 ng/ml (0-100), 3-methoxytyramine: 0.34 nmol/l (0-0.17). A 68-Ga-DOTA-Peptide PET/CT following 12 weeks of surgery demonstrated hypermetabolic lesions at left suprarenal area. A second open surgery was performed and lymph node metastases were detected (Figure 1). His cardiac functions ameliorated significantly following the removal of tumors. Genetic analysis for PPGL syndromes were negative for KIF1B, SDHB, NTRK1, TMEME127, VHL, RET, SDHD genes. Work-up is still pending for the mutations of SDHA, SDHC and SDHAF2 genes. Conclusion: Cathecolamine-induced cardiomyopathy is a rare entity associated with PPGL. Urgent recognition of related clinical signs and symptoms and detection of PPGL is lifesaving. It should be kept in mind in patients presenting with symptoms of heart failure, hypotension and multisystem crisis in the absence of coronary or valvular heart disease. Figure 1. Pheochromocytoma with lymph node metastasis. (H&E x100) [ABSTRACT FROM AUTHOR]

Giriş: Özgül öğrenme bozukluğunun(ÖÖB) patolojisi halen bilinmemesine rağmen nörobiyolojik bir temelinin olduğu düşünülmektedir. Hayvan model ve postmortem çalışmaları, beyin görüntüleme çalışmaları nöronal migrasyon ve nöronal büyümenin ÖÖB için önemli olduğunu göstermektedir. Daha önceki çalışmalarda ÖÖB ile ilişkili en az dokuz gen bölgesi saptanmıştır. Gen ekspresyon çalışmaları ve ÖÖB olan bireylerle yapılan çalışmalarda nörogenez, nöromigrasyon ve son dönemlerde siliyer biyogenez ile ilişkili bazı aday genlerin belirlenmesini sağlamıştır. Bazı yatkınlık genlerindeki tek nokta polimorfizmlerinin ÖÖB ile ilişkili olabileceği öngörülmüştür. Bu çalışmada, daha önce ÖÖB ile ilişkili olabileceği bildirilmiş bazı polimorfizmlerin ÖÖB olan olgu serisinde sıklıklarının araştırılması amaçlanmaktadır. Bu polimorfizmlerin ÖÖB'deki olası rolüne ilişkin ülkemizde yapılan ilk çalışmadır. Elde edilen sonuçlar ÖÖB etiyolojisinde genetik risk etkenlerinin rolüne ilişkin önemli katkılar sağlayacaktır. Yöntem: Çalışmamız, Aralık 2015- Mayıs 2016 tarihleri arasında Trakya Üniversitesi Tıp Fakültesi Çocuk ve Ergen Ruh Sağlığı ve Hastalıkları Anabilim Dalı Polikliniği'ne başvuran ve klinik değerlendirme sonucunda ÖÖB tanısı konan 6-16 yaşları arasındaki 102 olgu ve Trakya Üniversitesi Tıp Fakültesi Çocuk Sağlığı ve Hastalıkları Polikliniği'ne başvuran 161 sağlıklı kontrol ile yapılmıştır. Çalışmaya katılanlardan 2 ml periferik venöz kan örneği EDTA'lı tüpe alınıp kan örneklerinden genomik DNA izolasyonu yapıldıktan sonra rs4234898, rs11100040 ve rs2274305 SNP'lerinin genotip frekansları istatistiksel olarak analiz edilmiştir. Bulgular: Çalışma sonucunda DEHB eş tanısı olan ÖÖB olguları ile sadece ÖÖB tanısı olan olgular karşılaştırıldı ve rs2274305 GG genotipi açısından istatistiksel olarak anlamlı bir fark saptandı (p<0.05). Çalışmamızda rs2274305 SNP kız olgu ve kontrol gruplarıyla karşılaştırıldı ve AG ve GG genotipleri açısından istatistiksel açıdan sınırda anlamlılık saptanmıştır (p=0.05). Çalışmamızda herhangi bir eş tanısı olmayan ÖÖB'lilerde rs11100040 AG genotipinin ÖÖB ile ilişkili olduğu saptanmıştır. Ek olarak rs4234898 SNP olgu ve kontrol grubu arasında istatistiksel olarak anlamlı bir farklılık saptanmadı. Tartışma: rs2274305 SNP'nin DEHB birlikteliği olan ÖÖB için risk etkeni olabileceği, rs2274305 SNP'nin kız çocuklarda ÖÖB açısından risk etkeni olabileceği, rs11100040 SNP'nin ÖÖB için risk etkeni olabileceği rs4234898 SNP'nin ise risk etkeni olmadığı sonucuna varılmıştır. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is one of the most lethal cancers. It is mainly classified into 2 groups: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Extrapulmonary small cell carcinomas (EPSCC) are very rare. The Ras oncogene controls most of the cellular functions in the cell. Overall, 21.6% of human cancers contain a Kirsten Ras (KRAS) mutation. SCLC and EPSCC have several similar features but their clinical course is different. Aims: We investigated the KRAS mutation status in SCLC and EPSCC. Study design: Mutation research. Methods: Thirty-seven SCLC and 15 EPSCC patients were included in the study. The pathological diagnoses were confirmed by a second pathologist. KRAS analysis was performed in our medical genetic department. DNA isolation was performed with primary tumor tissue using the QIAamp DNA FFPE Tissue kit (Qiagen; Hilden, Germany) in all patients. The therascreen KRAS Pyro Kit 24 V1 (Qiagen; Hilden, Germany) was used for KRAS analyses. Results: Thirty-four (91.9%) of the SCLC patients were male, while 11 (73.3%) of the EPSCC l patients were female. SCLC was more common in males, and EPSCC in females (p=0.001). A KRAS mutation was found in 6 (16.2%) if SCLC patients. The most common mutation was Q61R (CAA>CGA). Among the 15 EPSCC patients, 2 had a KRAS mutation (13.3%). When KRAS mutant and wild type patients were compared in the SCLC group, no difference was found for overall survival (p=0.6). Conclusion: In previous studies, the incidence of KRAS mutation in SCLC was 1-3%; however, it was 16.2% in our study. Therefore, there may be ethnic and geographical differences in the KRAS mutations of SCLC. As a result, KRAS mutation should not be excluded in SCLC. [ABSTRACT FROM AUTHOR]

An abstract of the article "Investigation of BRAF Hotspot Mutations in Papillary Thyroid Tumor Samples," by Atakan Sezer and colleagues is presented.

Objectives: Papillary thyroid carcinoma is the most common type of thyroid cancer and is associated with BRAF (MIM 164757) mutations. Here, we report our 3 years of experience of pyrosequencing of BRAF hotspot regions in papillary thyroid carcinoma. Methods: Genomic DNA was isolated according to the manufacturer's protocol (QIAamp DNA FFPE Tissue Kit) from formalin-fixed paraffin-embedded tumor samples of 181 female and 81 male patients pre-diagnosed with papillary thyroid carcinoma. Pyrosequencing of BRAF mutation regions (codon 600 and codon 464-469) was performed as indicated in the protocol of the kit used (therascreen BRAF Pyro Kit, Qiagen). Results: BRAF mutations were defined in 33.3% of samples tested. V600E mutation was the most frequent mutation (31.98%). V600K mutation was present in only two of the samples (0.9%), whereas G466E mutation was defined only in one sample (0.45%). Percentages of the mutations between male and female patients were not significantly different. Conclusion: Presence of a BRAF mutation is commonly accepted as an additional prognostic feature of papillary thyroid carcinoma following tumor histology, primary tumor size, and invasion. Our results confirm the high frequency of BRAF mutations in papillary thyroid carcinoma. As a second point, we suggest that pyrosequencing is a practical method to study targeted mutations in the tumor samples. [ABSTRACT FROM AUTHOR]

Graft Versus Host Disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation (SCT). The MLC assay has been generally accepted as a standard test for determining HLA-D region compatibility. In this study, the MLC test has been carried out on the related recipient-donor couple who were prepared for allogeneic SCT and were found to be matched for HLA-A, -B, -Cw, DR, DQ but not for -DP. The result of the MLC test was positive. We observed that HLA-DP mismatch was responsible for the increased proliferation values in MLC test. [ABSTRACT FROM AUTHOR]

Graft Versus Host Disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation (SCT). The MLC assay has been generally accepted as a standard test for determining HLA-D region compatibility. In this study, the MLC test has been carried out on the re-lated recipient-donor couple who were prepared for allogeneic SCT and were found to be matched for HLA-A, -B, -Cw, DR, DQ but not for -DP. The result of the MLC test was positive. We observed that HLA-DP mismatch was responsible for the increased proliferation values in MLC test. [ABSTRACT FROM AUTHOR]