Yazar "Atli, Engin" seçeneğine göre listele
Listeleniyor 1 - 20 / 38
Sayfa Başına Sonuç
Sıralama seçenekleri
Öğe The Application of Next Generation Sequencing Maturity Onset Diabetes of the Young Gene Panel in Turkish Patients from Trakya Region(Galenos Yayincilik, 2021) Yalcintepe, Sinem; Comlek, Fatma Ozguc; Gurkan, Hakan; Demir, Selma; Atli, Emine Ikbal; Atli, Engin; Eker, DamlaObjective: 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.Öğe A Child with 5q Deletion and Accompanying Chiari 1 Malformation(Springer India, 2020) Atli, Emine Ikbal; Yalcintepe, Sinem; Atli, Engin; Demir, Selma; Gurkan, Hakan[Abstract Not Available]Öğe Chromosomal Microarray Analysis in Turkish Patients with Unexplained Developmental Delay and Intellectual Developmental Disorders(Turkish Neuropsychiatry Assoc-Turk Noropsikiyatri Dernegi, 2020) Gurkan, Hakan; Atli, Emine Ikbal; Atli, Engin; Bozatli, Leyla; Altay, Menguhan Araz; Yalcintepe, Sinem; Ozen, YaseminIntroduction: 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.Öğe Clinical Implications of Chromosome 16 Copy Number Variation(Karger, 2022) Atli, Emine Ikbal; Yalcintepe, Sinem; Atli, Engin; Demir, Selma; Mail, Cisem; Gurkan, HakanChromosome 16 is one of the gene-rich chromosomes; however, approximately 10% of the chromosome 16 sequence is composed of segmental copies, which renders this chromosome instable and predisposes it to rearrangements via frequent nonallelic homologous recombination. Microarray technologies have enabled the analysis of copy number variations (CNV), which may be associated with the risk of developing complex diseases. Through comparative genomic hybridisation in 1,298 patients, we detected 18 cases with chromosome 16 CNV. We identified 2recurrent CNV regions, including 1 at 16p13.11 in 4 patients and another at 16p11.2 in 7 patients. We also detected atypical chromosome 16 rearrangements in 7 patients. Furthermore, we noted an increased frequency of co-occurring genomic changes, supporting the two-hit hypothesis to explain the phenotypic variability in the clinical presentation of CNV syndromes. Our findings can contribute to the creation of a chromosome 16 disease map based on regions that may be associated with disease development.Öğe Comprehensive Genetic Analysis Results of TSC1/TSC2 Genes in Patients with Clinical Suspicion of Tuberous Sclerosis Complex and Definition of 3 Novel Variants(Galenos Publ House, 2021) Demir, Selma; Yalcintepe, Sinem; Atli, Engin; Yalcin, Yelda; Atli, Emine Ikbal; Eker, Damla; Karal, YaseminBackground: 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.Öğe The Correlation of Cystic Fibrosis Screening Test Results with Ultrasonographically Detected Fetal Anomalies in Prenatal Diagnosis(Galenos Publ House, 2023) Atli, Emine Ikbal; Atli, Engin; Demir, Selma; Yalcintepe, Sinem; Gurkan, HakanObjective: 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.Öğe Customised targeted massively parallel sequencing enables more precisely diagnosis of patients with epilepsy(Wiley, 2022) Atli, Emine Ikbal; Atli, Engin; Yalcintepe, Sinem; Demir, Selma; Kalkan, Rasime; Eker, Damla; Gurkan, HakanBackground Advancement in genetic technology has led to the identification of an increasing number of genes in epilepsy. This will provide a lot of information in clinical practice and improve the diagnosis and treatment of epilepsy. Aim To show the importance of genes in the next-generation sequencing (NGS) panel during the evaluation of epilepsy and to emphasise the importance of genetic studies in different populations for the evaluation of genes that cause disease. Methods This was a single-centre retrospective cohort study of 80 patients who underwent NGS testing with a customised epilepsy panel. Results In a total of 54 (67.5%) out of 80 patients, pathogenic or likely pathogenic variants and variants of uncertain significance (VOUS) were identified according to the American College of Medical Genetics and Genomics criteria. Pathogenic or likely pathogenic variants (n = 35) were identified in 29 (36.25%) out of 80 individuals. VOUS (n = 34) were identified in 28 (35%) out of 80 patients. Pathogenic, likely pathogenic and VOUS were most frequently identified in TSC2 (n = 11), SCN1A (n = 6) and TSC1 (n = 5) genes. Other common genes were KCNQ2 (n = 3), AMT (n = 3), CACNA1H (n = 3), CLCN2 (n = 3), MECP2 (n = 2), ASAH1 (n = 2) and SLC2A1 (n = 2). Conclusions NGS-based testing panels contribute to the diagnosis of epilepsy and might change the clinical management by preventing unnecessary and potentially harmful diagnostic procedures and management in patients. Thus, our results highlight the benefit of genetic testing in children suffering with epilepsy.Öğe Distal 3p Duplication and 22q13.3 Deletion with Severe Hypotonia Originating from a Paternal Balanced Translocation (3;22)(Karger, 2020) Yalcintepe, Sinem; Atli, Emine I.; Atli, Engin; Demir, Selma; Ciftdemir, Nukhet A.; Duran, Ridvan; Ozdemir, JansetIn this study, we present a case with distal 3p duplication and 22q13.3 deletion due to unbalanced meiotic segregation in her father carrying a balanced translocation. The 2-month-old girl was examined for her severe hypotonia, developmental delay, and mild dysmorphic appearance. Clinical features include broad forehead, hypertelorism, laterally extended eyebrows, long eyelashes, a depressed nasal root, bifid nasal tip, long philtrum, thin lips, posteriorly rotated ears, short neck, partial syndactyly of the right hand (fingers 3, 4) , and partial syndactyly of the right foot (toes 2, 3). After examination, the final karyotype was reported as: 46,XX,der(22)del(22)(qter)dup(3)(p22pter), and the array-CGH results showed arr[GRCh37] 3p26.3p22.1(93949_41518607)x3 and arr[GRCh37] 22q13.31q13.33(44554083_51224252)x1. The mother has a 46,XX karyotype, and her father carries a balanced translocation, 46,XY,t(3;22)(p26.3;q13.3). This is the first case with a distal 3p duplication and 22q13.3 deletion with severe hypotonia and developmental delay.Öğe First Report of Jacobsen Syndrome with Dextrocardia Diagnosed with del(11)(q24q25)(Karger, 2022) Yalcintepe, Sinem; Zhuri, Drenushe; Sezginer Guler, Hazal; Atli, Engin; Demir, Selma; Atli, Emine Ikbal; Mail, CisemJacobsen syndrome is a rare congenital disorder that is caused by the deletion of several genes in chromosome 11. A 10-year-old female with congenital heart disease, dextrocardia, and coarse facial appearance was examined in our medical genetics clinic. Chromosome analysis and array-CGH showed a copy number loss of 9 Mb in the 11q24.2q25 region. Herein, we report her clinical findings. This is the first case of Jacobsen syndrome with dextrocardia.Öğe The Frequency of SMN1, SMN2 Copy Numbers in 246 Turkish Cases Analyzed with MLPA Method(Thieme Medical Publ Inc, 2023) Yalcintepe, Sinem; Karal, Yasemin; Demir, Selma; Atli, Emine Ikbal; Atli, Engin; Eker, Damla; Mail, CisemThis study aimed to define the copy numbers of SMN1 and SMN2 genes and the diagnosis rate and carrier frequency of spinal muscular atrophy (SMA) in the Thrace region of Turkey. In this study, the frequency of deletions in exons 7 and 8 in the SMN1 gene and SMN2 copy numbers were investigated. A total of 133 cases with the preliminary diagnosis of SMA and 113 cases with the suspicion of being an SMA carrier from independent families were analyzed by multiplex ligation-dependent probe amplification method for SMN1 and SMN2 gene copy numbers.SMN1 homozygous deletions were detected in 34 patients (25.5%) of 133 cases with the suspicion of SMA. Cases diagnosed with SMA type I was 41.17% (14/34), 29.4% (10/34) with type II, 26.4% (9/34) with type III, and 2.94% (1/34) with type IV. The SMA carrier rate was 46.01% in 113 cases. In 34 SMA cases, SMN2 copy numbers were: two copies - 28 cases (82.3%), three copies - 6 cases (17.6%). SMN2 homozygous deletions were detected in 15% (17/113) of carrier analysis cases. The consanguinity rate of the parents was 23.5% in SMA diagnosed cases. In this study, we had a 25.5% of SMA diagnosis rate and 46% SMA carrier frequency. The current study also showed the relatively low consanguinity rate of the Thrace region, with 23.5% according to the east of Turkey.Öğe Genetic screening results of individuals with high risk BRCA-related breast/ovarian cancer in Trakya region of Turkey(Imprimatur Publications, 2020) Demir, Selma; Tozkir, Hilmi; Gurkan, Hakan; Atli, E. Ikbal; Yalcintepe, Sinem; Atli, Engin; Sezer, Y. AtakanPurpose: Pathogenic/likely pathogenic (P/LP) germline variations in BRCA1 and BRCA2 genes are responsible for the majority of hereditary breast and ovarian cancers. This study presents the BRCA1/BRCA2 sequencing and deletion duplication analyses results of of 493 participants (485 women, 8 men) selected based on the National Comprehensive Cancer Network (NCCN) guidelines. Methods: Next generation sequencing (NGS) and multiplex ligation-dependent probe amplification methods (MLPA) were used to define germline BRCA1/BRCA2 positivity. Results: Overall, the P/LP frequency of the participants was 17.8%. Five of the likely pathogenic variants were novel. The 5266dupC pathogenic variation, which is a founder mutation in the Ashkenazi Jewish population, was the most common variation among the patients, with a frequency of 5.47%. The pathogenic/likely pathogenic variation frequency was significantly higher (p=0.01) among clinically diagnosed familial cancer patisents than those participants without personal history of cancer but enrolled for BRCA1 testing due to familial risk. BRCA1/BRCA mutation positivity was significantly higher (p=0.000) among those who had at least one first- or second-degree relative with breast/ovarian cancer from patients who had no family history. BRCA1/BRCA2 mutation positivity was 69.23% between the patients who had personal history of both breast and ovarian cancer. Conclusion: Based on our findings, we suggest that sequencing all of the coding regions of the BRCA1/BRCA2 genes using NGS is a feasible approach for individuals who are at risk of developing BRCA-related cancer according to NCCN guidelines. The 5266dupC pathogenic variation, as the most common pathogenic variation in the Trakya region of Turkey, should be included if a targeted mutatin screening is planned.Öğe Genotype-phenotype correlations of pathogenic copy number variations on X chromosome detected by comparative genomic hybridization(Elsevier, 2022) Yalcintepe, Sinem; Atli, Engin; Atli, Emine Ikbal; Demir, Selma; Ozen, Yasemin; Mail, Cisem; Gurkan, HakanThe aim of this study was to present genotype-phenotype correlations of pathogenic copy number variations (CNVs) on X chromosome. Clinical and microarray data of the cases were collected. Conventional cytogenetics and CytoSure 4x180K oligonucleotide array (Agilent Technologies, Inc.) (Comparative Genomic Hybridization - CGH) was applicated to all cases. Molecular and clinical characterisation of these CNVs was performed in this study. 18 cases were included in this study for having a pathogenic CNV on X chromosome. The changes were reported pathologically by evaluating break points, anomaly size, number of involved genes and their functions and phenotypic correlations. 16 cases with pathogenic CNVs of X chromosome were examined with the clinical findings of multiple congenital anomalies, mental retardation, eosophageal atresia, duodenal atresia, autism spectrum disorder, hypogonadotropic hypogonadism, dysmorphic features, muscular dystrophy, hydrocephaly, neuromotor growth retardation, trigonocephaly, high risk of prenatal screening test, recurrent pregnancy loss with reciprocal translocation, fetal loss with multiple congenital anomalies. 2 cases were diagnosed as Turner Syndrome with rare karyotypes and array-CGH results. Our study contributes to the genotype/phenotype correlation with the delineation of laboratory criteria which help to classify the different CNVs detected on X chromosome. Atypical microdeletions/duplications allowed us to define minimal critical regions that could be responsible for specific clinical findings of the syndromes and to highlight some genes.Öğe Germline Pathogenic Variants Identified by Targeted Next-Generation Sequencing of Susceptibility Genes in Pheochromocytoma and Paraganglioma(Codon Publications, 2021) Yalcintepe, Sinem; Gurkan, Hakan; Korkmaz, Fatma Nur; Demir, Selma; Atli, Engin; Eker, Damla; Guler, Hazal SezginerThe aim of this study was to evaluate germline variant frequencies of pheochromocytoma and paraganglioma targeted susceptibility genes with next-generation sequencing method. Germline DNA from 75 cases were evaluated with targeted next-generation sequencing on an Illumina NextSeq550 instrument. KIF1B. RET, SDHB, SDHD, TMEM127, and VHL genes were included in the study, and Sanger sequencing was used for verifying the variants. The pathogenic/likely pathogenic variants were in the VHL, RET, SDHB, and SDHD genes, and the diagnosis rate was 24% in this study. Three different novel pathogenic variants were determined in five cases. This is the first study from Turkey, evaluating germline susceptibility genes of pheochromocytoma and paraganglioma with a detection rate of 24% and three novel variants. All patients with pheochromocytoma and paraganglioma need clinical genetic testing with expanded targeted gene panels for higher diagnosis rates.Öğe Homozygous Paternally Inherited ASPA Variant in a Patient with Canavan Disease(Karger, 2024) Yalcintepe, Sinem; Maras, Tuba; Kizilyar, Ilke; Guler, Hazal Sezginer; Zhuri, Drenushe; Atli, Engin; Ozen, YaseminIntroduction: Canavan disease is an autosomal recessive disorder that causes accumulation of N-acetyl ASPArtic acid in the brain due to ASPArtoacylase deficiency with homozygous or compound heterozygous pathogenic variants in the ASPA gene located on the short arm of chromosome 17. Clinical findings are hypotonia, progressive macrocephaly, deafness, nystagmus, blindness, and brain atrophy. Case Presentation: A one-year-old female case was evaluated in our medical genetics clinic for hypotonia, nystagmus, and strabismus. Chromosome analysis and array-comparative genomic hybridization showed no pathology. Clinical exome sequencing by next-generation sequencing was performed and a homozygous likely pathogenic variant NM_000049.4(ASPA):c.857C > A p.(Ala286Asp) was identified. Sanger sequencing of the parents showed that the index case had a homozygous genotype, the father was heterozygous and the mother had a wild genotype for the identified variant in ASPA. A single nucleotide polymorphism (SNP) array test was planned for the family to explain this homozygosity and a loss of maternal heterozygosity was determined in the 17p13.3-p13.2 region of the ASPA gene. Conclusion: In this report, we aimed to present the first case of Canavan disease with maternal loss of heterozygosity in the ASPA gene. (c) 2024 S. Karger AG, BaselÖğe Identification of a novel homozygous TBC1D24 mutation in a Turkish family with DOORS syndrome(Lippincott Williams & Wilkins, 2018) Atli, Engin; Gurkan, Hakan; Ulusal, Selma; Karal, Yasemin; Atli, Emine I.; Tozkir, Hilmi[Abstract Not Available]Öğe The Importance of Targeted Next-Generation Sequencing Usage in Cytogenetically Normal Myeloid Malignancies(Mattioli 1885, 2021) Atli, Emine Ikbal; Gurkan, Hakan; Atli, Engin; Kirkizlar, Hakki Onur; Yalcintepe, Sinem; Demir, Selma; Demirci, UfukAdvanced diagnostic methods give an advantage for the identification of abnormalities in myeloid malignancies. Various researchers have shown the potential importance of genetic tests before the disease's onset and in remission. Large testing panels prevent false-negative results in myeloid malignancies. However, the critical question is how the results of conventional cytogenetic and molecular cytogenetic techniques can be merged with NGS technologies. In this paper, we drew an algorithm for the evaluation of myeloid malignancies. To evaluate genetic abnormalities, we performed cytogenetics, molecular cytogenetics, and NGS testing in myeloid malignancies. In this study, we analyzed 100 patients admitted to the Medical Genetics Laboratory with different myeloid malignancies. We highlighted the possible diagnostic algorithm for cytogenetically normal cases. We applied NGS 141 gene panel for cytogenetically normal patients, and we detected two or more pathogenic variations in 61 out of 100 patients (61%). NGS's pathogenic variation detection rate varies in disease groups: they were present in 85% of A.M.L. and 23% of M. D.S. Here, we identified 24 novel variations out of total pathogenic variations in myeloid malignancies. A total of 18 novel variations were identified in A.M.L., and 6 novel variations were identified in M.D.S. Despite long turnaround times, conventional techniques are still a golden standard for myeloid malignancies but sometimes cryptic gene fusions or complex abnormalities cannot be easily identified by conventional techniques. In these conditions, advanced technologies like NGS are highly recommended.Öğe Investigating the Genetic Etiology of Pediatric Patients with Peripheral Hypotonia Using the Next-Generation Sequencing Method(Thieme Medical Publ Inc, 2022) Eker, Damla; Gurkan, Hakan; Karal, Yasemin; Yalcintepe, Sinem; Demir, Selma; Atli, Engin; Karasalihoglu, Serap T.Background Hypotonia occurs as a result of neurological dysfunction in the brain, brainstem, spinal cord, motor neurons, anterior horn cells, peripheral nerves, and muscles. Although the genotype-phenotype correlation can be established in 15 to 30% of patients, it is difficult to obtain a correlation in most cases. Aims This study was aimed to investigate the genetic etiology in cases of peripheral hypotonia that could not be diagnosed using conventional methods. Methods A total of 18 pediatric patients with peripheral hypotonia were included. They were referred to our genetic disorders diagnosis center from the Pediatric Neurology Department with a prediagnosis of hypotonia. A custom designed multigene panel, including ACTA1 , CCDC78 , DYNC1H1 , GARS , RYR1 , COL6A1 , COL6A2 , COL6A3 , FKRP , FKTN , IGHMBP2 , LMNA , LAMA2 , LARGE1 , MTM1 , NEM , POMGnT1 , POMT1 , POMT2 , and SEPN1 , was used for genetic analysis using next-generation sequencing (NGS). Results In our study, we found 13 variants including pathogenic (two variants in LAMA2) and likely pathogenic variants (three variants in RYR1 and POMGnT1) and variants of uncertain clinical significance (eight variants in RYR1, COL6A3, COL6A2, POMGnT1 and POMT1) in 11 (61%) out of 18 patients. In one of our patients, a homozygous, likely pathogenic c.1649G > A, p.(Ser550Asn) variant was defined in the POMGnT1 gene which was associated with a muscle-eye-brain disease phenotype. Conclusion The contribution of an in-house designed gene panel in the etiology of peripheral hypotonia with a clinical diagnosis was 5.5%. An important contribution with the clinical diagnosis can be made using the targeted multigene panels in larger samples.Öğe Investigation of Copy Number Variation by arrayCGH in Turkish Children and Adolescents Diagnosed with Autism Spectrum Disorders(Turkish Neuropsychiatry Assoc-Turk Noropsikiyatri Dernegi, 2018) Gorker, Isik; Gurkan, Hakan; Ulusal, Selma; Atli, Engin; Ayaz, Guclu; Ceylan, Cansin; Tozkir, HilmiAim: 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 microduptication 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.Öğe Investigation of Genes Associated With Atherosclerosis in Patients With Systemic Lupus Erythematosus(Turkish League Against Rheumatism, 2021) Balci, Mehmet Ali; Atli, Engin; Gurkan, HakanObjectives: 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.Öğe Investigation of Genetic Alterations in Congenital Heart Diseases in Prenatal Period(Thieme Medical Publ Inc, 2022) Atli, Emine Ikbal; Atli, Engin; Yalcintepe, Sinem; Demir, Selma; Kalkan, Rasime; Akurut, Cisem; Ozen, YaseminThe prenatal diagnosis of congenital heart disease (CHD) is important because of mortality risk. The onset of CHD varies, and depending on the malformation type, the risk of aneuploidy is changed. To identify possible genetic alterations in CHD, G-banding, chromosomal microarray or if needed DNA mutation analysis and direct sequence analysis should be planned. In present study, to identify genetic alterations, cell culture, karyotype analysis, and single nucleotide polymorphism, array analyses were conducted on a total 950 samples. Interventional prenatal genetic examination was performed on 23 (2, 4%, 23/950) fetal CHD cases. Chromosomal abnormalities were detected in 5 out of 23 cases (21, 7%). Detected chromosomal abnormalities were 10q23.2 deletion, trisomy 18, 8p22.3-p23.2 deletion, 8q21.3-q24.3 duplication, 11q24.2q24.5 (9Mb) deletion, and 8p22p12 (16.8Mb) deletion. Our study highlights the importance of genetic testing in CHD.