Tıp Fakültesi / Faculty of Medicine
Permanent URI for this collectionhttps://hdl.handle.net/11727/1403
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Item Evaluation of the Genetic Analysis Results in Infertile Patients with Non-Obstructive Azoospermia(2023) Sen, Erhan; Kizilkan, Yalcin; Duran, Mesut Berkan; Turunc, Tahsin; Sahin, Feride Iffet; Ozkardes, Hakan; 0000-0001-7308-9673; 0000-0002-7277-449X; AAC-7232-2020; AAH-1052-2020Objective: To evaluate the genetic analysis results of patients who referred to our clinic infertility and whom semen analysis revealed non -obstructive azoospermia (NOA).Materials and Methods: Among 994 patients who underwent a microscopic testicular sperm extraction (micro-TESE) operation for NOA, 497 patients who were tested for karyotype analysis and 450 patients who were tested for chromosome Y microdeletion were included in our study. The rates of Klinefelter syndrome (KS) and Y chromosome microdeletion, sperm retrieval rates (SRR) in these genetic anomalies and the factors affecting them were investigated. Additionally, the association between the age, duration of infertility, testicular size, serum follicle stimulant hormone (FSH) and testosterone levels of patients and sperm extraction rates of micro-TESE operations were also evaluated.Results: The overall SRR of NOA patients who underwent micro-TESE was 47.5%. Among 104 patients with KS, sperm was successfully found after micro-TESE in 22 (21.2%). Fourteen patients were diagnosed with the Y chromosome microdeletion and sperm was successfully found in 4 (28.6%) of them; while the duration of infertility did not affect the SRR after micro-TESE (p=0.712); age, testicular volume serum FSH and testosterone levels had a significant effect on the SRR (p<0.005).Conclusion: In this study, the SRR of patients who have chromosome Y microdeletion or KS, was found to be lower than other studies in the literature. This difference could be derived from the genetically tested population's structure, variance in the gene areas used for scanning and different demographic characteristics of different regions.Item Reclassification of Clinical Exome Data Leads To Significant Clinical Assessment Changes in Almost Half of the Patients(2023) Bayraktar, Umut Arda; Sahin, Feride Iffet; Polat, Mert; Terzi, Yunus KastmPurpose: With the global accumulation of genetic/clinical data, we are understanding the clinical significance of the reclassification of pathogenicity for gene variants. We hypothesized that this evolution in classification(s) may cause clinically-relevant discrepancies in the genetic risk assessment of subjects. In this study, we sought to reclassify the clinical exome sequence (CES) data of our patients to assess whether these changes would have clinical significance.Materials and Methods: The study included CES data of 23 cases diagnosed with cancer or familial cancer predisposition. The variants were first classified in 2020 and then reclassified a year after based on the ACMG database. Chart reviews were performed to record clinical history and interventions.Results: In the first classification of CES data, a total of 80 variants were identified as being not benign (26 likely pathogenic/pathogenic and 54 variants of undetermined significance (VUS)). The clinical significance of fifteen variants (19%) changed after reclassification in 10 patients (43%). The only upgraded variant was the c.9097 dup in exon 23 of BRCA2 gene (likely pathogenic to pathogenic). Fourteen variants were downgraded at reanalysis in 9 patients: from pathogenic to likely pathogenic (2 variants), pathogenic to VUS (2), likely pathogenic to VUS (4), and VUS to benign (6).Conclusion: Considering that the clinical significance of CES data changed due to reclassification in almost half of the studied patients, we believe genetic variant-related data should be assessed at regular intervals, regardless of follow-up status in the clinic.Item MLPA Method does not Always Confirm the Results of aCGH: A Study of KANSL1 Gene Deletion Patients(2022) Dincer, Selin Akad; Celik, Zerrin Yilmaz; Erol, Ilknur; Sahin, Feride Iffet; AAC-8356-2020Background: Microdeletion and microduplications are detected on chromosomes as a pathological subgroup of copy number variants of DNA. It has become easierto identify such chromosomal syndromes after use of array-based comparative genomic hybridization technology. One of them is the 17q21.31 microdeletion and microduplication syndrome. A 500-650 kb sized copy loss on 17q21.31 results in a phenotype which was described as Koolen-de Vries Syndrome including mental retardation, epilepsia, hypotonia and characteristic facial features. Today, we know that haplo-insufficiency of KANSL1 gene located in this region is responsible for these findings. A total of 30 patients with KANSL1 deletion detected during aCGH analyses were enrolled in the current study. All patients were analyzed by Multiplex Ligation-Dependent Probe Amplication (MLPA) method in order to confirm the results. Results: Three of the 30 patients had KANSL1 gene deletion detected by both methods and duplication was found in one patient. Conclusion: As a result of the study, we concluded that although new generation molecular methods enable us to obtain big and valuable data, each method has its own limitations and confirming the reults with another method increases test reliability. Using together of these methods are useful for the geneticists during diagnosis, clinical assessment and genetic counseling of patients.Item Comparison Of Diagnostic Criteria For Children With Familial Mediterranean Fever(2022) Onder, Esra Nagehan Akyol; Ozcan, Kudret Ebru; Sahin, Feride Iffet; Gulleroglu, Kaan Savas; Baskin, Esra; 35006379Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent attacks of fever and serositis. Diagnosis is made according to clinical findings and supported by genetic analysis. The most commonly used adult diagnostic criteria are the Tel-Hashomer criteria. Pediatric criteria for FMF diagnosis were described in 2009, but their reliability should be supported by additional reports. In this study, we aimed to compare the pediatric criteria and the Tel-Hashomer and 2019 Eurofever/PRINTO classification criteria using our FMF cohort. A total of 113 patients diagnosed with FMF were included. Demographic features and laboratory findings were retrospectively collected from the patients' files. The patients were evaluated with the Tel-Hashomer, pediatric and Eurofever/PRINTO classification criteria. At least two of five new pediatric criteria were as sensitive (89%) and specific (85%) as the Tel-Hashomer criteria (sensitivity 70%, specificity 96%). We also evaluated the Eurofever/PRINTO classification criteria using our cohort and found a sensitivity of 94% and specificity of 91%. Conclusion: Using pediatric criteria for the diagnosis of FMF in children is a feasible and simple approach that can diagnose the disease based on at least two criteria. Therefore, our study supports the use of pediatric criteria in FMF diagnosis of children. Our results also confirm that the Eurofever/PRINTO classification criteria can be successfully applied for the diagnosis of FMF due to their high sensitivity (94%) and specificity (91%). What is Known: center dot The FMF diagnosis is made according clinical findings and supported by genetic analysis. center dot The use of adult diagnostic criteria in pediatric FMF patients is controversial since classical clinical presentation is often absent in children. What is New: center dot Our study supports both the use of pediatric criteria and Eurofever/PRINTO classification criteria in clinical practice.Item The Role of Heredity and the Prevalence of Strabismus in Families with Accommodative, Partial Accommodative, and Infantile Esotropia(2020) Eroglu, Fatma Corak; Oto, Sibel; Sahin, Feride Iffet; Terzi, Yunus; Kaya, Ozge Ozer; Tekindal, Mustafa Agah; 0000-0003-0171-4200; 0000-0001-7308-9673; 0000-0001-5612-9696; 32631000; AAJ-4668-2021; AAC-7232-2020; B-4372-2018Objectives: To investigate the prevalence of strabismus in families of a proband with accommodative, partial accommodative, or infantile esotropia, and to evaluate the mode of inheritance and the role of consanguineous marriages in this prevalence. Materials and Methods: Families of probands with comitant strabismus were invited to participate in the study. The family members of 139 subjects with accommodative, 55 with partial accommodative, and 21 with infantile esotropia agreed to participate. Detailed family trees were constructed. The first- and second-degree relatives were invited for a complete ophthalmological examination, and 518 individuals from 168 families were evaluated. The role of consanguinity, the presence of tropia, phoria (>= 8 PD), microtropia, and hypermetropia (>= 3.00 D) among first- and second-degree relatives were analyzed. Results: A non-Mendelian pattern was found in 49 families (23%), an autosomal dominant pattern in 39 families (18%), and an autosomal recessive pattern in 6 families (3%). The prevalence of consanguineous marriages among parents of probands was 18.1%, 22.6%, and 14.3% in the accommodative, partial accommodative, and infantile esotropia groups, respectively (p=0.652). The prevalence of strabismus in first-degree relatives was 58.9%, 45.5%, and 38.1%, respectively (p=0.07). The prevalence of microtropia in probands' siblings was significantly higher in the accommodative esotropia group (p=0.034). Conclusion: Sporadic cases and non-Mendelian inheritance were more frequent than autosomal recessive inheritance. Autosomal recessive inheritance was found not to be frequent in consanguineous marriages. The prevalence of strabismus and microtropia was significantly higher in families of esotropia cases than in the general population.Item Investigation of ARHGEF12 Single Nucleotide Polymorphism in Hypercholesterolemia and Primary Open Angle Glaucoma(2020) Yaman, Derya; Takmaz, Tamer; Dincer, Selin Akad; Sahin, Feride Iffet; 0000-0001-7308-9673; AAK-2511-2021; AAC-7232-2020Objective:To investigate the effect of single nucleotide polymorphism rs58073046 A>G within the ARHGEF12 gene in patients with hypercholesterolemia and primary open angle glaucoma. Methods: Blood samples of 20 patients with high serum cholesterol and primary open angle glaucoma (Group 1), 20 sex and age matched healthy subjects (Group 2) as controls were enrolled to the study. The ARHGEF12 gene polymorphism was determined by polymerase chain reaction and DNA sequence analysis. The data were assessed by descriptive statics and Fisher exact x(2) test. Results: The homozygous wild type genotype (AA) was identified in 95 % of Group 1 versus 100 % of Group 2. The homozygous mutant genotype (GG), presented the highest prevelance in Group 1 (5%), although the difference was not statistically significant between groups (p=0.5). Conclusion: This is the first study to identify the role of ARHGEF12 gene variant in the risk of hypercholesterolemia and POAG. Our results showed that there is no association between rs58073046 A>G polymorphism and disease development.Item 22q13.3 Deletion Syndrome: An Underdiagnosed Cause of Mental Retardation(2015) Erol, Ilknur; Onay, Ozge Surmeli; Yilmaz, Zerrin; Ozer, Ozge; Alehan, Fusun; Sahin, Feride IffetPhelan-McDermid syndrome, also known as 22q13.3 deletion syndrome, is characterized by global developmental delay, absent or delayed speech, generalized hypotonia, and minor physical anomalies. The deletion typically involves the terminal band 22q13.3 and has been associated with both familial and de-novo translocations. We report the case of an 11-year-old Turkish girl with 22q13.3 deletion syndrome presenting with repeated seizures during the course of a rubella infection. We also review the clinical features of 22q13.3 deletion syndrome and emphasize the importance of considering a rare microdeletion syndrome for idiopathic mental retardation when results of a routine karyotype analysis are normal. To the best of our knowledge, this is the first reported case of a Turkish patient with isolated 22q13.3 deletion syndrome.Item Effect of Hereditary Hemochromatosis Gene H63D and C282Y Mutations on Iron Overload in Sickle Cell Disease Patients(2016) Terzi, Yunus Kasim; Balci, Tugce Bulakbasi; Boga, Can; Koc, Zafer; Celik, Zerrin Yilmaz; Ozdogu, Hakan; Karakus, Sema; Sahin, Feride Iffet; 27095682Objective: Hemochromatosis is an autosomal recessive disease that is one of the most important reasons for iron overload. Sickle cell disease is a hemoglobinopathy that occurs as a result of a homozygous mutation in the hemoglobin gene. Erythrocyte transfusion is frequently used in the treatment of this disease. Iron overload as a result of transfusion is important in the mortality and morbidity of sickle cell anemia patients as well as in other hemoglobinopathies. In this study, the effect of hemochromatosis gene (HFE) p.H63D and p.C282Y mutations on transfusion-related cardiac and liver iron overload in sickle cell disease patients who carry homozygous hemoglobin S mutation has been investigated. Materials and Methods: This is a prospective single-center cross-sectional study in patients with homozygous hemoglobin S mutation between the years 2008 and 2013. The patients were divided into two groups. The first group (group A, n=31) was receiving chelation therapy and the second group (group B, n=13) was not. Direct and indirect iron loads were analyzed by magnetic resonance imaging and biochemically, respectively. HFE gene mutations were analyzed by polymerase chain reaction-restriction fragment length polymorphism method. Statistical analyses were performed by independent samples t-test. Results: p.H63D mutation was detected in 10 (32.3%) patients in group A and in only 1 patient (7.7%) in group B. When the 2 groups were compared for iron overload, iron deposition in the liver was significantly higher in group B (p=0.046). In addition, in group A, iron deposition was significantly higher in HFE mutation carriers compared to patients without the mutation (p=0.05). Conclusion: Results of this study showed that HFE gene mutations are important in iron deposition in the liver in patients with sickle cell disease.Item BRCA1 and BRCA2 sequence variations detected with next-generation sequencing in patients with premature ovarian insufficiency(2016) Yilmaz, Nafiye Karakas; Karagin, Peren Hatice; Terzi, Yunus Kasim; Kahyaoglu, Inci; Yilmaz, Saynur; Erkaya, Salim; Sahin, Feride Iffet; 27403073Objective: Although the association between BRCA1 and BRCA2 gene mutations and breast and ovarian cancer is known, there is insufficient data about premature ovarian insufficiency (POI). However, several studies have reported that there might be a relationship between POI and BRCA1 and BRCA2 gene mutation. Therefore, in the present study, we aimed to investigate the role of BRCA1 and BRCA2 gene mutations in the etiology of POI in a Turkish population. Material and Methods: The cohort was classified into two groups: a study group, consisting of 56 individuals diagnosed with premature ovarian insufficiency (and who were younger than 40 years of age, had an antral follicle count <3-5, and FSH levels >12 IU/I), and a control group, consisting of 45 fertile individuals. A total of 101 individuals were analyzed by next-generation sequencing to detect BRCA1 and BRCA2 gene mutations. Results: We detected four new variations (p.T1246N and p.R1835Q in BRCA1 and p.I3312V and IVS-7T>A in BRCA2) that had not been reported before. Conclusion: We did not find an association between the BRCA1 and BRCA2 gene mutations and premature ovarian insufficiency. However, larger, functional studies are needed to clarify the association.