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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 BETA-GLOBIN GENE MUTATIONS AND MICRO-HAPLOTYPE POLYMOPHISMS OF BETA-THALASSEMIA PATIENTS IN TRAKYA POPULATION(John Wiley & Sons Inc, 2009) Gurkan, Hakan; Turgut, Burhan; Tozkir, Hilmi; Bozkurt, Gokay; Tekgunduz, Emre[Abstract Not Available]Öğe BLK pathway-associated rs13277113 GA genotype is more frequent in SLE patients and associated with low gene expression and increased flares(Springer London Ltd, 2017) Pamuk, Omer Nuri; Gurkan, Hakan; Pamuk, Gulsum Emel; Tozkir, Hilmi; Duymaz, Julide; Yazar, MetinWe aimed to evaluate the relationship between some important genetic variations and expressions of these genes in our SLE population. We also determined their association with clinical parameters. Eighty-four SLE patients (79 F, 5 M) and 105 healthy controls (98 F, 7 M) were included in the study. rs13277113, rs2736340, rs7829816, rs6983130, rs2613310, and rs704853 polymorphisms, gene expressions of Src family kinases (Blk, Hck, Lck, and Lyn), and Syk kinases (Syk, ZAP70) were studied by real-time PCR. The heterozygous genotypic pattern (GA) for rs13277113 polymorphism was more frequent in patients with SLE when compared to that in controls (48.8 vs. 31.4%, p = 0.035). Other genotype variants were similar in SLE patients and controls. In the SLE group, the heterozygous genotype for rs13277113 was significantly less frequent in active SLE patients (58.8 vs. 26.7%, p = 0.01). SLE flares according to the SELENA-SLEDAI flare index were significantly more frequent in GA (rs13277113) (70 vs. 37%) and CT (rs2736340) genotypes (66.7 vs. 35.2%) than those in other genotypes (p values < 0.01). The relative expression of Blk gene was significantly decreased in the SLE group as compared to that in controls (0.52 times, 95%CI 0.19-0.85). The gene expressions of Blk and ZAP70 were significantly lower in SLE patients who had flares according to the SELENA-SLEDAI flare index when compared to those in others (p values 0.01 and 0.017). We observed more frequent heterozygous GA genotypic pattern (rs13277113) in our SLE patients compared to that in controls; and it was associated with disease flares. Blk gene expression in SLE was lower, especially in relapsing patients.Öğe BLK Pathway-Associated rs13277113 GA Genotype Is More Frequent in Systemic Lupus Erythematosus Patients and Associated with Low Gene Expression and Increased Flares(Wiley, 2015) Pamuk, Omer Nuri; Gurkan, Hakan; Balci, Mehmet Ali; Tozkir, Hilmi; Duymaz, Julide; Sari, Gulce; Yazar, Metin[Abstract Not Available]Öğe Cardiofaciocutaneous Syndrome Phenotype in a Case with de novo KRAS Pathogenic Variant(Karger, 2020) Sanri, Aslihan; Gurkan, Hakan; Demir, SelmaCardiofaciocutaneous (CFC) syndrome is one of the developmental disorders caused by a dysregulation of the Ras/mitogen-activated protein kinase (MAPK) pathway. RASopathies share overlapping clinical features, making the diagnosis challenging, especially in the newborn period. The majority of CFC syndrome cases arise by a mutation in the BRAF, MAP2K1, MAP2K2, or (rarely) KRAS genes. Germline KRAS mutations are identified in a minority of CFC and Noonan syndrome cases. Here, we describe a patient with a KRAS mutation presenting with a CFC syndrome phenotype. The female patient was referred for genetic testing because of congenital exophthalmos. Her facial appearance is distinctive with a coarse face, exophthalmos, ptosis, downslanting palpebral fissures, hypertelorism, deep philtrum, downturned corners of the mouth, and a short neck. She suffered from feeding difficulties, poor weight gain, and developmental delay. The sequencing of the genes involved in the MAPK pathway (PTPN11, SOS1, RAF1, KRAS, NRAS, MAP2K1, SHOC2, CBL, and SPRED1) identified a heterozygous de novo NM_004985.4:c.173C>T (p.Thr58Ile) in the KRAS gene. Germline KRAS mutations have been identified in approximately 2% of the reported NS cases and less than 5% of the reported CFC syndrome cases. Because CFC and Noonan syndrome share clinical overlapping features, the phenotype caused by KRAS mutations is often difficult to assign to one of the 2 entities. The mutation that we detected in our patient was previously reported in a patient with an Noonan syndrome phenotype. However, our patient predominantly exhibits CFC clinical features. In our case, coarse facial appearance and severe developmental delay help discriminate CFC from Noonan syndrome. Thus, patient follow-up, especially for delayed motor milestones suspected from RASopathies, is important for the discrimination of overlapping conditions as in the abovementioned syndromes.Öğe A Case of Okur-Chung Neurodevelopmental Syndrome with a Novel, de novo Variant on the CSNK2A1 Gene in a Turkish Patient(Karger, 2023) Zhuri, Drenushe; Dusenkalkan, Fulya; Tunca Alparslan, Guzin; Gurkan, HakanIntroduction: Okur-Chung neurodevelopmental syndrome (OCNDS; #617062) has been associated with heterozygous mutations in the CSNK2A1 gene (*115440) mapped on the chromosome's 20p13 region. Case Presentation: The analysis was performed on a 2-year-old patient who was admitted to our genetic diseases evaluation center by his family with a complaint of hypotonia. We detected a heterozygous NM_177559.3 (CSNK2A1):c.1139_1140dupGG (p.Met381GlyfsTer32) variant in the CSNK2A1 gene from a whole-exome sequence analysis. Conclusion: The variant that we detected has not been reported in open-access databases to date, so it was evaluated as a novel likely pathogenic variant according to the ACMG-2015 criteria. No variant was detected upon segregation analysis of the patient's parents; therefore, the related variant was evaluated as de novo. In this study, we offer the first report of a pathogenic frameshift variant in the CSNK2A1 gene that has a relationship with OCNDS.Öğe A case report: 13q21-qter deletion with digital anomalies, duodenal atresia and anal atresia(Springer, 2015) Ozen, Yasemin; Gurkan, Hakan; Ozbek, Ulfet Vatansever; Atli, Emine Ikbal; Eker, Damla; Acunas, Betul[Abstract Not Available]Öğe CASP10, LEF1, BCL2 genes are hypomethylated and CDKN2B is hypermethylated in chronic lymphocytic leukemia(Taylor & Francis Ltd, 2015) Pamuk, Gulsum Emel; Uyanik, Mehmet Sevki; Gurkan, Hakan; Duymaz, Julide; Tozkir, Hilmi; Pamuk, Omer Nuri[Abstract Not Available]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 Chronic myeloid leukaemia after chemoradiotherapy for solid malignancies(Wolters Kluwer Medknow Publications, 2020) Baysal, Mehmet; Ulutas, Gulcin; Gokyer, Ali; Umit, Elif; Atli, Emine Ikbal; Kirkizlar, Onur; Gurkan, HakanHaematological malignancies associated with chemoradiotherapy (CRT) are often acute myeloid leukaemias and myelodysplastic syndromes. Chronic myeloid leukaemia (CML) has been reported rarely in these situations. Cytogenetics of CRT-associated CML is not different from de novo CML, and there are not enough data about its prognosis. We report two patients who had CRT because of lung cancer and squamous cell carcinoma of head and neck, who subsequently developed CML.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 Complex Nature of Neural Tube Defects: A Regional Experience(2018) Turhan, Emrah; Varol, Fusun G.; Gurkan, Hakan; Sayın, N. CenkOBJECTIVE: The underlying gene-environment interaction of fetal neural tube defects is affected byseveral factors including geography, ethnicity and time. Local features of fetal neural tube defects weredescribed.STUDY DESIGN: A prospective cohort study of 48 fetal neural tube defects in a single tertiary medicalcenter at the northwestern region of Turkey (2013-2015) was done via ultrasound, magnetic resonanceimaging (MRI), conventional karyotyping, maternal methylenetetrahydrofolate reductase c.677C>T(rs1801133) single-nucleotide polymorphism and maternal serum levels of folic acid, vitamin B12 andzinc. For comparison of means, a Student’s T-Test was used.RESULTS: The prevalence of neural tube defects was 11.4 per 10000 births (48/42000) in northwesternTurkey. The defects on the cranium (n=23; 47.9%) and spine (n=25; 52.1%) were ultrasonographicallydetected. MRI did not give additional benefit over the ultrasonography. The ratio of associated anomaliesin neural tube defect group was 25%. Two fetal neural tube defects with Down syndrome were remarkable. The rate of homozygous methylenetetrahydrofolate reductase c.677C > T SNPs among the mothersof neural tube defect fetuses (n=20) was 15%. Comparing with gestationally matched healthy pregnancies, although maternal BMIs and periconceptional folate intake of neural tube defect group were significantly different, maternal serum folic acid, vitamin B12 and zinc levels were similar.CONCLUSION: The northwestern region appeared to be a relatively low prevalence area of Turkey forfetal neural tube defects. Any association with maternal serum folic acid, vitamin B12 and zinc levelscould not be shown in this region.Öğe Concepts of Double Hit and Triple Hit Disease in Multiple Myeloma, Entity and Prognostic Significance(Nature Portfolio, 2020) Baysal, Mehmet; Demirci, Ufuk; Umit, Elif; Kirkizlar, Hakki Onur; Atli, Emine Ikbal; Gurkan, Hakan; Gulsaran, Sedanur KaramanRisk assessment in newly diagnosed multiple myeloma patients (NDMM) is the first and the most crucial determinant of treatment. With the utilization of FISH analysis as a part of routine practice, high risk Multiple Myeloma (MM) is defined as having at least one of the mutations related with poor prognosis including; t(4;14) t(14;16), t(14;20), del 17p, p53 mutation, gain 1q and del 1p. M-Smart MM risk stratification guideline by Mayo Clinic has proposed a concept similar to high grade lymphomas. Having two of the high risk genetic abnormalities were defined as double hit MM and having any three as triple hit MM. Based on these definitions which may bring a much more clinically relatable understanding in MM prognosis, we aimed to assess our database regarding these two concepts and their probable significance in terms of outcome and prognosis. We retrospectively evaluated 159 newly diagnosed multiple myeloma patients and their clinical course. Among these patients; twenty-four patients have one high risk determinant and also seven and two patients were classified as double hit MM and triple hit MM respectively. Overall survival (OS) of the patients with double hit MM was 6 months, 32.0 months for patients with single high risk abnormality and 57.0 months for patients with no high risk abnormality. Univariate analysis showed that Double Hit and Triple Hit MM is a predictive of low OS. Hazard Ratio of patients with one high risk abnormality was 1.42, double-hit MM patients was 5.55, and triple-hit MM patients was 7.3. Despite the development of novel drugs and their effects of prolonging survival, the treatment has not been individualized. Understanding the biology of each patient as a unique process will be the success of the treatment. As it is known that some MM patients harbor high risk genetic abnormalities according to FISH analysis, we can continue the argument that some patients bring an even higher risk and that can be defined as double or triple hit MM.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 CXCL12 rs18011157 polymorphism in patients with non-Hodgkin's lymphoma: Is it associated with poor outcome?(Wolters Kluwer Medknow Publications, 2018) Pamuk, Gulsum Emel; Tozkir, Hilmi; Uyanik, Mehmet Sevki; Gurkan, Hakan; Duymaz, Julide; Pamuk, Omer NuriObjective: We studied CXCL12-related rs18011157 polymorphism in non-Hodgkin lymphoma (NHL) patients. We also determined the effect of this polymorphism on clinical features and outcome of NHL. Methods: We included 90 NHL patients (54 males, 36 females) and 88 healthy controls (54 males, 34 females). CXCL12-related rs18011157 polymorphism was determined by polymerase chain reaction. Results: rs18011157 polymorphism was significantly more frequent in NHL patients with GA genotype than in healthy controls (37.8% vs. 20.5%, P = 0.011). The frequency of patients with initially high lactate dehydrogenase (LDH) level (65.8% vs. 38.5%) and extranodal involvement (61.1% vs. 43.8%) was significantly higher in the GA plus AA genotype groups when considered altogether (P = 0.01 and 0.09). Poor prognostic factors in univariate analysis were the presence of B symptoms, initially high International Prognostic Index (IPI), splenomegaly, nonresponse to first-line therapy, the presence of early relapse, and carrying A allele (GA plus AA genotypes). The independent prognostic factors in multivariate analysis were only early relapse and an initially high IPI score. Discussion: CXCL12 rs1801157 polymorphism which was found to be associated with extranodal involvement and increased LDH in NHL might be a marker of poor prognosis in patients with GA and AA genotypes. Conclusions: CXCL12-related rs18011517 polymorphism was more frequent in NHL patients: it might be associated with NHL pathogenesis and outcome.Öğe The Effect of TGFB1 and CD14 Gene Polymorphisms on the Clinical Findings of Cystic Fibrosis in Turkish Patients(Kamla-Raj Enterprises, 2016) Temurhan, Sonay; Tamay, Zeynep; Gurkan, Hakan; Akgul, Sebahat; Ozceker, Deniz; Kekik, Cigdem; Cagatay, PenbeSignificant effects of several modifying genes on the clinical features of cystic fibrosis (CF) have been reported. In the present study, the researchers investigated the effects of transforming growth factor beta 1 (TGFB1) and cluster of differentiation 14 (CD14) polymorphisms on the clinical status of patients with CF. The present study included sixty-five patients with CF and eighty five healthy controls with no pulmonary disease. Single-nucleotide polymorphisms in the TGFB1 gene (rs1800469, rs1800470, rs8179181) were studied using DNA sequence analyses; the CD14 gene polymorphism rs2569190 was evaluated using restriction fragment length polymorphism analysis. The frequency of rs1800469 (TT genotype) was significantly higher in the healthy controls than in the patients with CF. Thus, the TT genotype may be protective against CF. Although rs8179181 (CT genotype) may have an overall negative effect, this genotype may have a favourable effect on growth parameters. However, these results should be confirmed in larger studies.Öğe THE FREQUENCY OF Y CHROMOSOME MICRODELETIONS AND CYTOGENETIC ABNORMALITIES IN CASES WITH MALE INFERTILITY FROM THRACE REGION: SINGLE CENTER EXPERIENCE(Istanbul Univ, Fac Medicine, Publ Off, 2021) Yalcintepe, Sinem; Eker, Damla; Gurkan, HakanObjective: 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.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.
