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Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease and usually involves the skin, musculoskeletal system, and kidneys. More than 30 genes have been to monogenic lupus, so far. Monogenic lupus is often characterized by an early-onset, similar family history, and syndromic appearance. Herein we present a pediatric patient with DNASE1L3 deficiency, suffering from both urticarial skin lesions, recurrent hemoptysis, and renal involvement, eventually diagnosed as this rare monogenic lupus. The patient suffered from recurrent urticarial rash and hemoptysis since the age of 15 months of age. He had microscopic hematuria, mild proteinuria, hypocomplementemia, and positive antinuclear antibody, anti-dsDNA, and antineutrophil cytoplasmic antibodies. Renal biopsy yielded immunocomplex glomerulonephritis. Due to early-onset, similar sibling history and consanguineous parents, we suspected monogenic lupus and performed whole-exome sequencing, which further revealed a homozygous T97Ifs*2 mutation (NM_004944.4: c.290_291delCA/p.Thr97Ilefs*2) in DNASE1L3 gene. In conclusion, DNASE1L3 deficiency should be thought when juvenile SLE occurs with early disease-onset, pulmonary hemorrhage, glomerulonephritis, and recurrent urticarial rash along with ANCA positivity.
Rabia Miray Kisla Ekinci; Sibel Balci; Dilek Ozcan; Bahriye Atmis; Atil Bisgin. Monogenic lupus due to DNASE1L3 deficiency in a pediatric patient with urticarial rash, hypocomplementemia, pulmonary hemorrhage, and immune-complex glomerulonephritis. European Journal of Medical Genetics 2021, 64, 104262 .
AMA StyleRabia Miray Kisla Ekinci, Sibel Balci, Dilek Ozcan, Bahriye Atmis, Atil Bisgin. Monogenic lupus due to DNASE1L3 deficiency in a pediatric patient with urticarial rash, hypocomplementemia, pulmonary hemorrhage, and immune-complex glomerulonephritis. European Journal of Medical Genetics. 2021; 64 (9):104262.
Chicago/Turabian StyleRabia Miray Kisla Ekinci; Sibel Balci; Dilek Ozcan; Bahriye Atmis; Atil Bisgin. 2021. "Monogenic lupus due to DNASE1L3 deficiency in a pediatric patient with urticarial rash, hypocomplementemia, pulmonary hemorrhage, and immune-complex glomerulonephritis." European Journal of Medical Genetics 64, no. 9: 104262.
Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease (COVID-19) caused by the novel coronavirus SARS-coronavirus 2 (CoV-2). To combat the devastating spread of SARS-CoV-2, extraordinary efforts from numerous laboratories have focused on the development of effective and safe vaccines. Traditional live-attenuated or inactivated viral vaccines are not recommended for immunocompromised patients as the attenuated virus can still cause disease via phenotypic or genotypic reversion. Subunit vaccines require repeated dosing and adjuvant use to be effective, and DNA vaccines exhibit lower immune responses. mRNA vaccines can be highly unstable under physiological conditions. On the contrary, naturally antigenic viral vectors with well-characterized structure and safety profile serve as among the most effective gene carriers to provoke immune response via heterologous gene transfer. Viral vector-based vaccines induce both an effective cellular immune response and a humoral immune response owing to their natural adjuvant properties via transduction of immune cells. Consequently, viral vectored vaccines carrying the SARS-CoV-2 spike protein have recently been generated and successfully used to activate cytotoxic T cells and develop a neutralizing antibody response. Recent progress in SARS-CoV-2 vaccines, with an emphasis on gene therapy viral vector-based vaccine development, is discussed in this review.
Atil Bisgin; Ahter D. Sanlioglu; Yunus Emre Eksi; Thomas S. Griffith; Salih Sanlioglu. Current Update on Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Development with a Special Emphasis on Gene Therapy Viral Vector Design and Construction for Vaccination. Human Gene Therapy 2021, 32, 541 -562.
AMA StyleAtil Bisgin, Ahter D. Sanlioglu, Yunus Emre Eksi, Thomas S. Griffith, Salih Sanlioglu. Current Update on Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Development with a Special Emphasis on Gene Therapy Viral Vector Design and Construction for Vaccination. Human Gene Therapy. 2021; 32 (11-12):541-562.
Chicago/Turabian StyleAtil Bisgin; Ahter D. Sanlioglu; Yunus Emre Eksi; Thomas S. Griffith; Salih Sanlioglu. 2021. "Current Update on Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Development with a Special Emphasis on Gene Therapy Viral Vector Design and Construction for Vaccination." Human Gene Therapy 32, no. 11-12: 541-562.
Variants in the myogenesis-regulating glycosidase (MYORG) gene which is known as the first autosomal recessive gene that has been associated with primary familial brain calcification (AR-PFBC). Although adult patients have been reported, no pediatric case has been reported until now. Herein, we review the clinical and radiological features of all AR- PFBC patients with biallelic variants in the MYORG gene who were reported until now, and we report the youngest patient who has a novel homozygous variant. Since the first identification of the MYORG gene in 2018, 74cases of MYORG variants related to AR-PFBC were evaluated. The ages of symptom onset of the patients ranged between 7.5 and 87 years. The most frequent clinical courses were speech impairment, movement disorder and cerebellar signs. All patients showed basal ganglia calcification usually bilaterally with different severities. Conclusion; herein, we reported the first pediatric patient in the literature who had a novel homozygous variant in the MYORG gene with mild clinic findings.
Leman Tekin Orgun; Şeyda Besen; Özlem Sangün; Atıl Bisgin; Özlem Alkan; Ilknur Erol. First pediatric case with primary familial brain calcification due to a novel variant on the MYORG gene and review of the literature. Brain and Development 2021, 43, 789 -797.
AMA StyleLeman Tekin Orgun, Şeyda Besen, Özlem Sangün, Atıl Bisgin, Özlem Alkan, Ilknur Erol. First pediatric case with primary familial brain calcification due to a novel variant on the MYORG gene and review of the literature. Brain and Development. 2021; 43 (7):789-797.
Chicago/Turabian StyleLeman Tekin Orgun; Şeyda Besen; Özlem Sangün; Atıl Bisgin; Özlem Alkan; Ilknur Erol. 2021. "First pediatric case with primary familial brain calcification due to a novel variant on the MYORG gene and review of the literature." Brain and Development 43, no. 7: 789-797.
The aim of this study was to summarize the experiences of a single medical center for genetic diagnosis and treatment of prenatal patients. This study includes a retrospective data analysis of 2843 prenatally investigated cases using invasive methods during a 6-year period (2013–2019) at a single tertiary care center. Chromosomal abnormalities were detected in 80 out of 1221 amniotic fluid samples;,178 out of 1608 chorionic villus samples, and 1 out of 14 cordocentesis samples. The most common chromosomal abnormality was trisomy 21. At least one mutation was detected in 63 of the 152 molecular tests performed on fetuses. Clinical procedures such as ultrasounds and genetic tests are able to provide a better clinical follow-up for pregnant women about the possible congenital anomalies or any genetic condition, with proper genetic counseling and testing methodology.
Sevcan Tuğ Bozdoğan; Selim Büyukkurt; Sinem Özer; Atıl BİŞGİN. Evaluation of the results of patients who applied to the Çukurova University, Medical Genetics Department for prenatal diagnosis and determination of genetic counseling principles. TURKISH JOURNAL OF MEDICAL SCIENCES 2021, 51, 657 -660.
AMA StyleSevcan Tuğ Bozdoğan, Selim Büyukkurt, Sinem Özer, Atıl BİŞGİN. Evaluation of the results of patients who applied to the Çukurova University, Medical Genetics Department for prenatal diagnosis and determination of genetic counseling principles. TURKISH JOURNAL OF MEDICAL SCIENCES. 2021; 51 (2):657-660.
Chicago/Turabian StyleSevcan Tuğ Bozdoğan; Selim Büyukkurt; Sinem Özer; Atıl BİŞGİN. 2021. "Evaluation of the results of patients who applied to the Çukurova University, Medical Genetics Department for prenatal diagnosis and determination of genetic counseling principles." TURKISH JOURNAL OF MEDICAL SCIENCES 51, no. 2: 657-660.
Next Generation Sequencing (NGS) has uncovered hundreds of common and rare genetic variants involved in complex and rare diseases including immune deficiencies in both an autosomal recessive and autosomal dominant pattern. These rare variants however, cannot be classified clinically, and common variants only marginally contribute to disease susceptibility. In this study, we evaluated the multi-gene panel results of Common Variable Immunodeficiency (CVID) patients and argue that rare variants located in different genes play a more prominent role in disease susceptibility and/or etiology. We performed NGS on DNA extracted from the peripheral blood leukocytes from 103 patients using a panel of 19 CVID-related genes: CARD11, CD19, CD81, ICOS, CTLA4, CXCR4, GATA2, CR2, IRF2BP2, MOGS, MS4A1, NFKB1, NFKB2, PLCG2, TNFRSF13B, TNFRSF13C, TNFSF12, TRNT1 and TTC37. Detected variants were evaluated and classified based on their impact, pathogenicity classification and population frequency as well as the frequency within our study group. NGS revealed 112 different (a total of 227) variants with under 10% population frequency in 103 patients of which 22(19.6%) were classified as benign, 29(25.9%) were classified as likely benign, 4(3.6%) were classified as likely pathogenic and 2(1.8%) were classified as pathogenic. Moreover, 55(49.1%) of the variants were classified as variants of uncertain significance. We also observed different variant frequencies when compared to population frequency databases. Case–control data is not sufficient to unravel the genetic etiology of immune deficiencies. Thus, it is important to understand the incidence of co-occurrence of two or more rare variants to aid in illuminating their potential roles in the pathogenesis of immune deficiencies.
Atil Bisgin; Ozge Sonmezler; Ibrahim Boga; Mustafa Yilmaz. The impact of rare and low-frequency genetic variants in common variable immunodeficiency (CVID). Scientific Reports 2021, 11, 1 -8.
AMA StyleAtil Bisgin, Ozge Sonmezler, Ibrahim Boga, Mustafa Yilmaz. The impact of rare and low-frequency genetic variants in common variable immunodeficiency (CVID). Scientific Reports. 2021; 11 (1):1-8.
Chicago/Turabian StyleAtil Bisgin; Ozge Sonmezler; Ibrahim Boga; Mustafa Yilmaz. 2021. "The impact of rare and low-frequency genetic variants in common variable immunodeficiency (CVID)." Scientific Reports 11, no. 1: 1-8.
Objectives Hereditary Hypophosphatemic Rickets (HHR) is a heterogeneous group of disorders characterized by hypophosphatemia. Although the X-linked dominant HHR is the most common form, the genetic etiology of HHR is variable. Recently, developed next-generation sequencing techniques may provide opportunities for making HHR diagnosis in a timely and efficient way. Methods We investigated clinical and genetic features for 18 consecutive probands and their 17 affected family members with HHR. All patient’s clinical and biochemical data were collected. We first analyzed a single gene with Next-generation sequencing if the patients have a strong clue for an individual gene. For the remaining cases, a Hypophosphatemic Rickets gene panel, including all known HHR genes by Next-generation sequencing, was employed. Results We were able to diagnosis all of the consecutive 35 patients in our tertiary care center. We detected nine novel and 10 previously described variants in PHEX (9; 50%), SLC34A3 (3; 17%), ENPP1 (3; 17%), SLC34A1 (1; 5%), CLCN5 (1; 5%), and DMP1 (1; 5%). Conclusions To delineate the etiology of HHR cases in a cost and time-efficient manner, we propose single gene analysis by next-generation sequencing if findings of patients indicate a strong clue for an individual gene. If that analysis is negative or for all other cases, a Next-generation Sequence gene panel, which includes all known HHR genes, should be employed.
Ihsan Turan; Sevcan Erdem; Leman Damla Kotan; Semine Ozdemir Dilek; Mehmet Tastan; Fatih Gurbuz; Atıl Bişgin; Aysun Karabay Bayazıt; Ali Kemal Topaloglu; Bilgin Yuksel. Experience with the targeted next-generation sequencing in the diagnosis of hereditary hypophosphatemic rickets. Journal of Pediatric Endocrinology and Metabolism 2021, 34, 639 -648.
AMA StyleIhsan Turan, Sevcan Erdem, Leman Damla Kotan, Semine Ozdemir Dilek, Mehmet Tastan, Fatih Gurbuz, Atıl Bişgin, Aysun Karabay Bayazıt, Ali Kemal Topaloglu, Bilgin Yuksel. Experience with the targeted next-generation sequencing in the diagnosis of hereditary hypophosphatemic rickets. Journal of Pediatric Endocrinology and Metabolism. 2021; 34 (5):639-648.
Chicago/Turabian StyleIhsan Turan; Sevcan Erdem; Leman Damla Kotan; Semine Ozdemir Dilek; Mehmet Tastan; Fatih Gurbuz; Atıl Bişgin; Aysun Karabay Bayazıt; Ali Kemal Topaloglu; Bilgin Yuksel. 2021. "Experience with the targeted next-generation sequencing in the diagnosis of hereditary hypophosphatemic rickets." Journal of Pediatric Endocrinology and Metabolism 34, no. 5: 639-648.
STRUCTURED SUMMARY Introduction Urinary tract stone disease (UTSD) is seen with increasing frequency in children, and genetic, metabolic and environmental factors are known to play a role in its etiology. Since it is a genetically heterogeneous disease, we investigated the multigene panel and metabolic evaluation together. Material and Method Forty-eight pediatric patients that underwent surgery for UTSD and were followed up in the Department of Urology of Çukurova University Faculty of Medicine between March 2016 and July 2019 were included in the study. Children with known metabolic diseases were excluded.A detailed history was taken from each patient, and presence of a positive family history was questioned. Blood and urine samples were obtained, and metabolic evaluation was performed. In addition, 2 cc peripheral blood samples were collected from selected patients to perform DNA isolation at Çukurova University Adana Genetic Diseases Diagnosis and Treatment Center. The analysis of the obtained sequence data was performed. Results Of the 48 children included in the study, 29 (60.4%) were male and 19 (39.6%) were female. The mean age was 60 ± 50 (12-192) months. It was observed that 28 (58.3%) of the patients included in the study had a positive family history.As a result of the next-generation sequencing studies conducted with the multigene panel, a total of 21 clinically significant variants in eight different genes were identified with the bioinformatics analysis on the data on which quality control was performed. The weighted distribution of the 21 variants according to the genes was as follows: five variants (23.8%) in the SLC3A1 gene, four (19%) in SLC6A20, and three (14.3%) in SLC7A9 and SLC26A1. The clinical reporting of the disease etiology and/or variants with prognostic significance determined as a result of the performed analyses was completed by field experts in accordance with international standards. The visuals of the detected variants are presented in Figure. Conclusion In pediatric cases with UTSD, it is important to determine the underlying metabolic and genetic risk factors in order to prevent recurrence and apply the most effective treatment.
Elnur Ziyadov; Atil Bisgin; Mutlu Deger; Nebil Akdogan; Volkan Izol; I. Atilla Aridogan; Nihat Satar. Determination of the etiology of pediatric urinary stone disease by multigene panel and metabolic screening evaluation. Journal of Pediatric Urology 2021, 1 .
AMA StyleElnur Ziyadov, Atil Bisgin, Mutlu Deger, Nebil Akdogan, Volkan Izol, I. Atilla Aridogan, Nihat Satar. Determination of the etiology of pediatric urinary stone disease by multigene panel and metabolic screening evaluation. Journal of Pediatric Urology. 2021; ():1.
Chicago/Turabian StyleElnur Ziyadov; Atil Bisgin; Mutlu Deger; Nebil Akdogan; Volkan Izol; I. Atilla Aridogan; Nihat Satar. 2021. "Determination of the etiology of pediatric urinary stone disease by multigene panel and metabolic screening evaluation." Journal of Pediatric Urology , no. : 1.
Background This case series includes longitudinal clinical data of ten patients with Morquio A syndrome from south and southeastern parts of Turkey, which were retrospectively collected from medical records. All patients received enzyme replacement therapy (ERT). Clinical data collected included physical appearance, anthropometric data, neurological and psychological examinations, cardiovascular evaluation, pulmonary function tests, eye and ear-nose-throat examinations, endurance in the 6-min walk test and/or 3-min stair climb test, joint range of motion, and skeletal investigations (X-rays, bone mineral density). Results At the time of ERT initiation, two patients were infants (1.8 and 2.1 years), five were children (3.4–7.1 years), and three were adults (16.5–39.5 years). Patients had up to 4 years follow-up. Most patients had classical Morquio A, based on genotypic and phenotypic data. Endurance was considerably reduced in all patients, but remained relatively stable or increased over time in most cases after treatment initiation. Length/height fell below normal growth curves, except in the two infants who started ERT at ≤ 2.1 years of age. All patients had skeletal and/or joint abnormalities when ERT was started. Follow-up data did not suggest improvements in skeletal abnormalities, except in one of the younger infants. Nine patients had corneal clouding, which resolved after treatment initiation in the two infants, but not in the other patients. Hepatomegaly was reported in seven patients and resolved with treatment in five of them. Other frequent findings at treatment initiation were coarse facial features (N = 9), hearing loss (N = 6), and cardiac abnormalities (N = 6). Cardiac disease deteriorated over time in three patients, but did not progress in the others. Conclusions Overall, this case series with Morquio A patients confirms clinical trial data showing long-term stabilization of endurance after treatment initiation across ages and suggest that very early initiation of ERT optimizes growth outcomes.
Sebile Kılavuz; Sibel Basaran; Deniz Kor; Fatma Derya Bulut; Sevcan Erdem; Hüseyin Tuğsan Ballı; Muhammed Dağkıran; Atil Bisgin; Halise Neslihan Önenli Mungan. Morquio A syndrome and effect of enzyme replacement therapy in different age groups of Turkish patients: a case series. Orphanet Journal of Rare Diseases 2021, 16, 1 -10.
AMA StyleSebile Kılavuz, Sibel Basaran, Deniz Kor, Fatma Derya Bulut, Sevcan Erdem, Hüseyin Tuğsan Ballı, Muhammed Dağkıran, Atil Bisgin, Halise Neslihan Önenli Mungan. Morquio A syndrome and effect of enzyme replacement therapy in different age groups of Turkish patients: a case series. Orphanet Journal of Rare Diseases. 2021; 16 (1):1-10.
Chicago/Turabian StyleSebile Kılavuz; Sibel Basaran; Deniz Kor; Fatma Derya Bulut; Sevcan Erdem; Hüseyin Tuğsan Ballı; Muhammed Dağkıran; Atil Bisgin; Halise Neslihan Önenli Mungan. 2021. "Morquio A syndrome and effect of enzyme replacement therapy in different age groups of Turkish patients: a case series." Orphanet Journal of Rare Diseases 16, no. 1: 1-10.
Background Neuroendocrine tumours (NETs) arise from hormone-producing or nervous system cells and can develop from anywhere in the body. They have heterogeneous origins from skin to gastrointestinal track and a complicated histology. Thus, there is an inevitable need for genomic profiling to determine the exact genetics of each tumour for prognosis and treatment strategies to overcome the disease’s complexity. For this purpose, next-generation-sequencing (NGS) is the most reliable methodology for both germ-line and somatic studies to make a clinical diagnosis. In this study, we analyse liquid biopsies, formalin fixed paraffin embedded (FFPE) tissues, and peripheral blood samples for their ability to provide information for actionability. Methods A customized multi-gene panel comprised of Succinate Dehydrogenase Complex Iron Sulfur Subunit B (SDHB), Succinate Dehydrogenase Complex Subunit C (SDHC), Cell Division Cycle 73(CDC73), Calcium Sensing Receptor (CASR), Platelet Derived Growth Factor Receptor Alpha (PDGFRA), Succinate Dehydrogenase Complex Flavoprotein Subunit A (SDHA), Ret Proto-Oncogene (RET), Succinate Dehydrogenase Complex Assembly Factor 2(SDHAF2), Menin 1(MEN1), Succinate Dehydrogenase Complex Subunit D (SDHD), MYC Associated Factor X (MAX) and Protein Kinase CAMP-Dependent Type I Regulatory Subunit Alpha (PRKAR1A) genes was constructed to assess multiple specimen types including: 3 liquid biopsies, 6 FFPE tissues, and 26 peripheral blood samples from 35 unique NET patients. Quality-control and bioinformatics analyses were performed using QCI-Analyze and QCI-Interpret. Results The three liquid biopsies and the 6 FFPE tissue samples were evaluated for somatic mutations; while the 26 peripheral blood samples were analysed using the germ-line pipeline. Five (55.6%) of the nine patients that were studied for somatic changes carried actionable mutations related to therapy sensitivities. Through the germ-line studies, we observed a 50% positivity rate for disease predisposition with 16 variants classified according to ACMG (American College of Medical Genetics) Standards and Guidelines. Conclusions Genomic profiling medicine is an emerging area of clinical oncology and has become crucial for disease and patient management by providing a precision approach; this is especially true for rare diseases including rare cancers such as NETs. Notably, this study emphasized the relevance of multiple distinctive biological sample types for use in the genetic testing of cancers to help with the choice of therapy to maximize the likelihood of a positive clinical outcome.
Guney Isa Burak; Sonmezler Ozge; Mujde Cem; Buyukdereli Gulgun; Dogruca Yapar Zeynep; Bisgin Atil. The emerging clinical relevance of genomic profiling in neuroendocrine tumours. BMC Cancer 2021, 21, 1 -7.
AMA StyleGuney Isa Burak, Sonmezler Ozge, Mujde Cem, Buyukdereli Gulgun, Dogruca Yapar Zeynep, Bisgin Atil. The emerging clinical relevance of genomic profiling in neuroendocrine tumours. BMC Cancer. 2021; 21 (1):1-7.
Chicago/Turabian StyleGuney Isa Burak; Sonmezler Ozge; Mujde Cem; Buyukdereli Gulgun; Dogruca Yapar Zeynep; Bisgin Atil. 2021. "The emerging clinical relevance of genomic profiling in neuroendocrine tumours." BMC Cancer 21, no. 1: 1-7.
Background: Cystic fibrosis (CF) is the most common worldwide, life-shortening multisystem hereditary disease, with an autosomal recessive inheritance pattern caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The national newborn screening (NBS) program for CF has been initiated in Turkey since 2015. If the immunoreactive trypsinogen (IRT) is elevated (higher than 70 μg/L in the second control) and confirmed by sweat test or clinical findings, genetic testing is performed. The aims of this study are to emphasize the effect of NBS on the status of genetic diagnosis centers with the increasing numbers of molecular testing methods, and to determine the numbers and types of CFTR mutations in Turkey. Methods: The next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) results of 1595 newborns, who were referred to Cukurova University Adana Genetic Diseases Diagnosis and Treatment Center (AGENTEM) for molecular genetic testing, were evaluated with positive CF NBS program results since 2017. Results: According to the results; 560 (35.1%) of the 1595 patients carried at least 1 (one) CF-related variant, while 1035 patients (64.9%) had no mutation. Compound heterozygosity for two mutations was the most common in patients, while two detected variants were homozygote in 14 patients. A total of 161 variants were detected in 561 patients with mutations. Fifteen novel variants that have not been previously reported were found. Moreover, p.L997F was identified as the most frequent pathogenic mutation that might affect the IRT measurements used for the NBS. The distribution of mutation frequencies in our study showed a difference from those previously reported; for example, the well-known p.F508del was the third most common (n = 42 alleles), rather than the first. The most striking finding is that 313 cases had a pathogenic variant together with the V470M variant, which might have a cumulative effect on CF perpetuation. Conclusion: This study is the first to determine the mutational spectrum of CFTR in correlation with the NBS program in the Turkish population. NBS for CF raises issues regarding screening in diverse populations, both medical and non-medical benefits, and carrier identification. Through the lens of NBS, we focused on the integrated diagnostic algorithms and their effect on the results of genetic testing.
Sevcan Bozdogan; Cem Mujde; Ibrahim Boga; Ozge Sonmezler; Abdullah Hanta; Cagla Rencuzogullari; Dilek Ozcan; Derya Altintas; Atil Bisgin. Current Status of Genetic Diagnosis Laboratories and Frequency of Genetic Variants Associated with Cystic Fibrosis through a Newborn-Screening Program in Turkey. Genes 2021, 12, 206 .
AMA StyleSevcan Bozdogan, Cem Mujde, Ibrahim Boga, Ozge Sonmezler, Abdullah Hanta, Cagla Rencuzogullari, Dilek Ozcan, Derya Altintas, Atil Bisgin. Current Status of Genetic Diagnosis Laboratories and Frequency of Genetic Variants Associated with Cystic Fibrosis through a Newborn-Screening Program in Turkey. Genes. 2021; 12 (2):206.
Chicago/Turabian StyleSevcan Bozdogan; Cem Mujde; Ibrahim Boga; Ozge Sonmezler; Abdullah Hanta; Cagla Rencuzogullari; Dilek Ozcan; Derya Altintas; Atil Bisgin. 2021. "Current Status of Genetic Diagnosis Laboratories and Frequency of Genetic Variants Associated with Cystic Fibrosis through a Newborn-Screening Program in Turkey." Genes 12, no. 2: 206.
Inflammatory bowel diseases, familial adenomatous polyposis (FAP) and colorectal cancer (CRC) are associated with alterations of the intestinal microbiota. However, few data are available on the perpetuation of FAP and ulcerative colitis (UC) in relation to microbial dysbiosis. This study evaluated the UC and genetically confirmed FAP patients’ gut microbial balance in concordance to clinical outcome. Fecal materials (average mass of 0.54 g) were collected from three FAP and five UC patients to compare with healthy individuals as control group. Genomic materials of micro-biota were isolated for next generation sequencing of 16S rRNA that was performed by using QIAseq 16S/ITS panel in Illumina Miseq Platform. Data processing and bioinformatics analysis were performed via CLC Genomic Workbench bioinformatics tool. The comparison between FAP, UC and control group revealed an alteration in the intestinal microbial composition. More in details, relative abundance of class levels showed statistical significance differences among FAP, UC and control groups. Our preliminary data focused on the explanation of how dysbiosis can lead to inflammation and drive processes together with host genetic profile that leads to colorectal carcinogenesis.
Abdullah Hanta; Ahmet Rencuzogullari; Ibrahim Boga; Ismail Cem Eray; Atil Bisgin. Changes of Gut Microbiota in Fap and UC Patients in Mediteranean Region of Turkey: An –Omic Landscape to Be Discovered. 2020, 1 .
AMA StyleAbdullah Hanta, Ahmet Rencuzogullari, Ibrahim Boga, Ismail Cem Eray, Atil Bisgin. Changes of Gut Microbiota in Fap and UC Patients in Mediteranean Region of Turkey: An –Omic Landscape to Be Discovered. . 2020; ():1.
Chicago/Turabian StyleAbdullah Hanta; Ahmet Rencuzogullari; Ibrahim Boga; Ismail Cem Eray; Atil Bisgin. 2020. "Changes of Gut Microbiota in Fap and UC Patients in Mediteranean Region of Turkey: An –Omic Landscape to Be Discovered." , no. : 1.
Objectives Congenital nephrogenic diabetes insipidus (NDI) is a rare hereditary disorder which is characterized by unresponsiveness to arginine vasopressin (AVP) in collecting ducts and leads to polyuria and polydipsia. The wide clinical spectrum of congenital NDI can cause difficulties in early diagnosis. We aimed to evaluate clinical prognosis of children with congenital NDI in long-term period. Methods Nineteen children with congenital NDI followed up in Pediatric Nephrology Department were enrolled to the study. This study is a single-center retrospective study, which reports clinical follow-up and genetic results of children with congenital NDI. Results Presenting symptoms of patients were mostly dehydration and fever due to polyuria and polydipsia. Four male patients had bilateral nonobstructive hydroureteronephrosis (HUN) and neurogenic bladder which requires clean intermittent catheterization (CIC). One patient had intracranial calcification which is a rarely seen complication in congenital NDI due to recurrent hypernatremic dehydration and severe brain dehydration. The causative mutations were identified in all patients. The identified mutations in six of them (31.6%) were hemizygous mutations in AVPR2 gene and homozygous mutations of AQP2 gene in the rest 13 cases (68.4%). More than that, four of these mutations (two in AVPR2 and two in AQP2) were novel mutations. Noncompliance with the treatments is associated with high risk of morbidity due to neurogenic bladder and chronic kidney disease (CKD). Conclusions The prognosis of congenital NDI is good when diagnosis can be made early and treatment is started immediately. Genetic counseling and prenatal testing for hereditary diseases are recommended especially in regions with relatively higher rates of consanguineous marriages.
Bahriye Atmis; Aysun Karabay Bayazit; Engin Melek; Atil Bisgin; Ali Anarat. From infancy to adulthood: challenges in congenital nephrogenic diabetes insipidus. Journal of Pediatric Endocrinology and Metabolism 2020, 33, 1019 -1025.
AMA StyleBahriye Atmis, Aysun Karabay Bayazit, Engin Melek, Atil Bisgin, Ali Anarat. From infancy to adulthood: challenges in congenital nephrogenic diabetes insipidus. Journal of Pediatric Endocrinology and Metabolism. 2020; 33 (8):1019-1025.
Chicago/Turabian StyleBahriye Atmis; Aysun Karabay Bayazit; Engin Melek; Atil Bisgin; Ali Anarat. 2020. "From infancy to adulthood: challenges in congenital nephrogenic diabetes insipidus." Journal of Pediatric Endocrinology and Metabolism 33, no. 8: 1019-1025.
The lack of awareness of patient risk factors, failure to obtain adequate family history, was discussed by clinical experience in prenatal testing of hypophosphatasia with a novel variant in the ALPL gene identified in the index case of the family.
Atil Bisgin; Ibrahim Boga; Cihan Cetin; Selim Buyukkurt. Identification of a novel homozygous variant in the alkaline phosphate ( ALPL ) gene associated with hypophosphatasia. Clinical Case Reports 2020, 8, 1719 -1721.
AMA StyleAtil Bisgin, Ibrahim Boga, Cihan Cetin, Selim Buyukkurt. Identification of a novel homozygous variant in the alkaline phosphate ( ALPL ) gene associated with hypophosphatasia. Clinical Case Reports. 2020; 8 (9):1719-1721.
Chicago/Turabian StyleAtil Bisgin; Ibrahim Boga; Cihan Cetin; Selim Buyukkurt. 2020. "Identification of a novel homozygous variant in the alkaline phosphate ( ALPL ) gene associated with hypophosphatasia." Clinical Case Reports 8, no. 9: 1719-1721.
Hereditary C2 deficiency is the most common early complement deficiency and characterized by recurrent infections and autoimmunity despite most patients are also asymptomatic. Type I hereditary C2 deficiency is caused by a heterozygous deletion in C2 gene resulting in early stop codon and lack of C2 production. Clinical spectrum may vary and pure nephrological involvement without the presence of recurrent infections is scarce in hereditary C2 deficiency. We report here a previously healthy 14-year-old boy presenting recurrent self-limited macroscopic hematuria and persistently low serum C4 levels, diagnosed as having type I hereditary C2 deficiency with confirming a novel heterozygote deletion (c.1567 + 22_1567 + 43del) in C2 gene. He has been remained asymptomatic for the next 18 months. Since the diagnosis of C2 deficiency was made in the absence of organ-threatening involvement such as immune complex-mediated glomerulonephritis, we think that early diagnosis and optimal follow-up may improve life-span of the patients with hereditary early complement deficiencies.
Rabia Miray Kisla Ekinci; Ibrahim Altun; Atil Bisgin; Bahriye Atmis; Derya Ufuk Altintas; Sibel Balcı. Recurrent macroscopic hematuria in a pediatric patient: is it early to diagnose as having type I hereditary C2 deficiency? CEN Case Reports 2020, 9, 1 -3.
AMA StyleRabia Miray Kisla Ekinci, Ibrahim Altun, Atil Bisgin, Bahriye Atmis, Derya Ufuk Altintas, Sibel Balcı. Recurrent macroscopic hematuria in a pediatric patient: is it early to diagnose as having type I hereditary C2 deficiency? CEN Case Reports. 2020; 9 (4):1-3.
Chicago/Turabian StyleRabia Miray Kisla Ekinci; Ibrahim Altun; Atil Bisgin; Bahriye Atmis; Derya Ufuk Altintas; Sibel Balcı. 2020. "Recurrent macroscopic hematuria in a pediatric patient: is it early to diagnose as having type I hereditary C2 deficiency?" CEN Case Reports 9, no. 4: 1-3.
Intrauterine infections with the pathogens, including toxoplasmosis, other (syphilis, varicella, mumps, parvovirus, and HIV), rubella, cytomegalovirus, and herpes simplex (TORCH) in susceptible individuals during pregnancy, result in microcephaly, white matter disease, cerebral atrophy, and calcifications in the fetus. Pseudo-TORCH syndrome is an umbrella term, consisting of several syndromes, resultant from different genetic alterations and pathogenetic mechanisms. Band-like calcification with simplified gyration and polymicrogyria (BLC-PMG) is one of these conditions, resultant from biallelic mutations in the OCLN gene, located in the chromosome 5q13.2. OCLN gene encodes occludin, a tight junction protein, which is expressed in the endothelia. The absence of occludin in the developing brain subsequently results in abnormal blood-brain barrier, thus immune-cell mediated tissue damage and cortical malformation. Herein, we present a pediatric patient who had progressive microcephaly, spasticity, multi-drug resistant epilepsy, PMG and intracranial band-type calcifications, accompanied by central diabetes insipidus and renal dysfunction. Whole exome sequencing revealed a homozygote W58Ffs*10 (c.173_194del) frameshift mutation in the OCLN gene. Of 34 BLC-PMG cases with demonstrable OCLN mutations, only three had renal manifestations, which is responsible for the majority of the demises. This is the first case diagnosed as having central diabetes insipidus and responded to desmopressin treatment to the best of our knowledge, however, this clinical improvement could not prevent the patient from renal dysfunction. The patient deceased at four years of age from sepsis, therefore early diagnosis, optimal follow-up for renal involvement and infection prevention measures are necessary for the patients with BLC-PMG.
Faruk Ekinci; Riza Dincer Yildizdas; Ozden Ozgur Horoz; Ozlem Herguner; Atil Bisgin. A homozygote frameshift mutation in OCLN gene result in Pseudo-TORCH syndrome type I: A case report extending the phenotype with central diabetes insipidus and renal dysfunction. European Journal of Medical Genetics 2020, 63, 103923 .
AMA StyleFaruk Ekinci, Riza Dincer Yildizdas, Ozden Ozgur Horoz, Ozlem Herguner, Atil Bisgin. A homozygote frameshift mutation in OCLN gene result in Pseudo-TORCH syndrome type I: A case report extending the phenotype with central diabetes insipidus and renal dysfunction. European Journal of Medical Genetics. 2020; 63 (6):103923.
Chicago/Turabian StyleFaruk Ekinci; Riza Dincer Yildizdas; Ozden Ozgur Horoz; Ozlem Herguner; Atil Bisgin. 2020. "A homozygote frameshift mutation in OCLN gene result in Pseudo-TORCH syndrome type I: A case report extending the phenotype with central diabetes insipidus and renal dysfunction." European Journal of Medical Genetics 63, no. 6: 103923.
Familial Mediterranean Fever (FMF) is the most common hereditary autoinflammatory disorder characterized by recurrent fever and serositis episodes. Identification of low penetrant or heterozygous MEFV mutations in clinically diagnosed FMF patients did raise a concern on whether epigenetic or environmental factors play an additional role in FMF pathogenesis. We aimed to investigate the expression profile of apoptosis-related miRNAs in FMF and their influence on clinical manifestations in the present study. 191 pediatric FMF patients and 31 healthy children included in the study. Expressions of 33 apoptosis-related, circulating cell-free miRNAs were evaluated by a quantitative polymerase chain reaction, statistically calculated within ΔΔCt values and fold changes were evaluated by Welch T test, in which p < 0.05 were considered to be significant. Nineteen miRNAs, including let-7a-5p, let-7c, let-7 g-5p, miR-15b-5p, miR-16-5p, miR-17-5p, miR-23a-3p, miR-24-3p, miR-25-3p, miR-26a-5p, miR-26b-5p, miR-27a-3p, miR-29c-3p, miR-30a-5p, miR-30d-5p, miR-30e-5p, miR-106b-5p, miR-146a-5p, and miR-195-5p, were found down-regulated; miR-15a-5p, miR-29b-3p, miR-181a-5p, miR-181b-5p, miR-181c-5p, miR-214-3p, and miR-365a-3p were up-regulated in FMF patients. In detail, these miRNAs were similar among FMF patients in terms of genotype, colchicine response, and having an inflammatory attack during analysis. We found that 26 apoptosis-related circulating miRNAs were deregulated in children with FMF. Thus, we speculate that these miRNAs have a role in FMF pathogenesis via apoptotic mechanisms.
Emin Murat Karpuzoglu; Rabia Miray Kisla Ekinci; Sibel Balci; Atil Bisgin; Mustafa Yilmaz. Altered expression of apoptosis-related, circulating cell-free miRNAs in children with familial Mediterranean fever: a cross-sectional study. Rheumatology International 2020, 41, 103 -111.
AMA StyleEmin Murat Karpuzoglu, Rabia Miray Kisla Ekinci, Sibel Balci, Atil Bisgin, Mustafa Yilmaz. Altered expression of apoptosis-related, circulating cell-free miRNAs in children with familial Mediterranean fever: a cross-sectional study. Rheumatology International. 2020; 41 (1):103-111.
Chicago/Turabian StyleEmin Murat Karpuzoglu; Rabia Miray Kisla Ekinci; Sibel Balci; Atil Bisgin; Mustafa Yilmaz. 2020. "Altered expression of apoptosis-related, circulating cell-free miRNAs in children with familial Mediterranean fever: a cross-sectional study." Rheumatology International 41, no. 1: 103-111.
Molybdenum cofactor deficiency is a rare neurometabolic disease that is usually characterized by seizures, abnormal muscle tonus, developmental delay and poor nutrition, and is seen soon after birth. Pyloric stenosis causes serious vomiting in the first months of life. The presence of neurologic damage in molybdenum cofactor deficiency and possible abnormal innervations may cause pyloric stenosis; however, the pathogenesis is unclear. Pyloric stenosis with molybdenum cofactor deficiency has been described in two cases. Herein, we report the third case and suggest that hypertrophic pyloric stenosis should be kept in mind as a clinical manifestation of molybdenum cofactor deficiency.
Mehmet Satar; Ahmet Ibrahim Kurto; Atıl Bi. Coexistence of molybdenum cofactor deficiency type A and hypertrophic pyloric stenosis, a new case. Türk Pediatri Arşivi 2020, 56, 78 -80.
AMA StyleMehmet Satar, Ahmet Ibrahim Kurto, Atıl Bi. Coexistence of molybdenum cofactor deficiency type A and hypertrophic pyloric stenosis, a new case. Türk Pediatri Arşivi. 2020; 56 (1):78-80.
Chicago/Turabian StyleMehmet Satar; Ahmet Ibrahim Kurto; Atıl Bi. 2020. "Coexistence of molybdenum cofactor deficiency type A and hypertrophic pyloric stenosis, a new case." Türk Pediatri Arşivi 56, no. 1: 78-80.
Tumor necrosis factor receptor associated periodic fever syndrome (TRAPS) is caused by heterozygote mutations in TNFRSF1A, characterized by recurrent inflammatory attacks. In this report, we described two patients with different heterozygote mutations in TNFRSF1A. Patient 1, a 15-year-old male, had suffered from recurrent fever attacks accompanied by abdominal pain, eye manifestations, and myalgia with increased acute phase reactants since the age of 6-month. He had been unsuccessfully treated with colchicine for having familial Mediterranean fever without an identifiable MEFV mutation since the age of 4-year. At the age of 15 years, he was diagnosed with immunoglobulin (Ig) A nephropathy due to massive proteinuria and renal biopsy findings. Next generation sequencing revealed NM_001065.3: c.236C>T; p. (Thr79Met); T50M heterozygote mutation in TNFRFS1A. He was treated with methylprednisolone and cyclosporine for IgA nephropathy, thereafter with canakinumab for TRAPS. Patient 2, a 17-year-old female, had recurrent arthritis attacks accompanied by increased acute phase reactants for the last two months. She had neither fever attacks nor rashes or myalgia. Her physical examination was normal between attacks. Magnetic resonance imaging of both knees and ankles showed no signs of chronic arthritis. MEFV analyzes showed no mutation. Next generation sequencing revealed NM_001065.3: c.362G>A; p.(Arg121Gln); R92Q heterozygote mutation in TNFRFS1A. Arthritis attacks were treated successfully with ibuprofen thereafter. In conclusion, we wish to emphasize the diversity of the clinical manifestations between these two patients with distinct sequence variants in TNFRSF1A. Moreover, we presented a rare manifestation of TRAPS, IgA nephropathy.
Sibel Balci; Rabia Miray Kisla Ekinci; Engin Melek; Bahriye Atmis; Atıl Bisgin; Mustafa Yilmaz. Phenotypic variability in two patients with tumor necrosis factor receptor associated periodic fever syndrome emphasizes a rare manifestation: Immunoglobulin A nephropathy. European Journal of Medical Genetics 2019, 63, 103780 .
AMA StyleSibel Balci, Rabia Miray Kisla Ekinci, Engin Melek, Bahriye Atmis, Atıl Bisgin, Mustafa Yilmaz. Phenotypic variability in two patients with tumor necrosis factor receptor associated periodic fever syndrome emphasizes a rare manifestation: Immunoglobulin A nephropathy. European Journal of Medical Genetics. 2019; 63 (4):103780.
Chicago/Turabian StyleSibel Balci; Rabia Miray Kisla Ekinci; Engin Melek; Bahriye Atmis; Atıl Bisgin; Mustafa Yilmaz. 2019. "Phenotypic variability in two patients with tumor necrosis factor receptor associated periodic fever syndrome emphasizes a rare manifestation: Immunoglobulin A nephropathy." European Journal of Medical Genetics 63, no. 4: 103780.
Deficiency of Adenosine Deaminase 2 (DADA2) is a monogenic autoinflammatory disorder characterized by livedo reticularis, skin ulcers, subcutaneous rash, aphthous ulcers, and leukocytoclastic vasculitis, neurological signs such as early onset stroke and polyneuropathy. A minority of DADA2 patients suffer from severe cytopenia and lymphoproliferation. Herein, we report an adolescent patient, followed up as having a hematological disorder for many years, eventually diagnosed as having DADA2. In view of the presence of elevated acute phase reactants, hepatosplenomegaly, low IgM level, lymphopenia, anemia, and neutropenia, and a subtle neurological involvement we considered DADA2 diagnosis. The diagnosis was confirmed by identification of a novel L451W mutation in CECR1 gene. The patient has been successfully treated with etanercept, monthly intravenous immunoglobulin replacement, and low-dose methylprednisolone. In conclusion, although the absence of skin and neurological findings, low IgM levels, and persistent lymphopenia should lead the physicians to consider DADA2 in patients with particularly complicated hematological abnormalities.
Rabia Miray Kisla Ekinci; Sibel Balcı; Atil Bisgin; Ilgen Sasmaz; Goksel Leblebisatan; Faruk Incecik; Mustafa Yilmaz. A homozygote novel L451W mutation in CECR1 gene causes deficiency of adenosine deaminase 2 in a pediatric patient representing with chronic lymphoproliferation and cytopenia. Pediatric Hematology and Oncology 2019, 36, 376 -381.
AMA StyleRabia Miray Kisla Ekinci, Sibel Balcı, Atil Bisgin, Ilgen Sasmaz, Goksel Leblebisatan, Faruk Incecik, Mustafa Yilmaz. A homozygote novel L451W mutation in CECR1 gene causes deficiency of adenosine deaminase 2 in a pediatric patient representing with chronic lymphoproliferation and cytopenia. Pediatric Hematology and Oncology. 2019; 36 (6):376-381.
Chicago/Turabian StyleRabia Miray Kisla Ekinci; Sibel Balcı; Atil Bisgin; Ilgen Sasmaz; Goksel Leblebisatan; Faruk Incecik; Mustafa Yilmaz. 2019. "A homozygote novel L451W mutation in CECR1 gene causes deficiency of adenosine deaminase 2 in a pediatric patient representing with chronic lymphoproliferation and cytopenia." Pediatric Hematology and Oncology 36, no. 6: 376-381.
Certain genetic predisposition factors, such as BRCA1 and BRCA2 mutations play a pivotal role in familial breast cancer development in both males and females. Due to this, the importance and necessity of genetic screening to identify mutations affecting the population is paramount. Undergoing genetic screenings allows for a more knowledgeable risk assessment for the patients and their care providers. The aim of this study was to evaluate the prevalence of BRCA1/BRCA2 mutated genes in the Turkish population among unselected patients. To identify the molecular markers, we utilized a gene panel analysis consisting of BRCA1 and BRCA2 genes, with a next generation sequencing platform (MiSeq System, Illumina). Sequencing was performed using leukocyte DNA from breast cancer patients. In‐silico analysis for novel mutations was carried out using SIFT, PolyPhen2 and MutationTaster. BRCA1 and BRCA2 pathogenic variants were identified in 18 of 129 (14%) patients among the study population; of those 18 patients, seven (39%) were found in the BRCA1 gene and 11 (61%) in the BRCA2 gene. Ten of the eleven BRCA2 variants (90%) were novel mutations. Four of ten (40%) of the novel mutations were determined to be deleterious and six out of ten (60%) were identified as single nucleotide variations. Clinically significant mutations of the BRCA1/BRCA2 genes are related to an increased susceptibility for breast cancer. There is however, little known about BRCA mutations amongst the general population. Thus, it is important that patients are able to undergo genetic screenings and counseling. This also allows for greater care from health care providers and can only facilitate disease prevention which in turn can lead to a decreased cancer morbidity rate.
Atil Bisgin; Ibrahim Boga; Orcun Yalav; Ozge Sonmezler; Sevcan Tug Bozdogan. BRCAmutation characteristics in a series of index cases of breast cancer selected independent of family history. The Breast Journal 2019, 25, 1029 -1033.
AMA StyleAtil Bisgin, Ibrahim Boga, Orcun Yalav, Ozge Sonmezler, Sevcan Tug Bozdogan. BRCAmutation characteristics in a series of index cases of breast cancer selected independent of family history. The Breast Journal. 2019; 25 (5):1029-1033.
Chicago/Turabian StyleAtil Bisgin; Ibrahim Boga; Orcun Yalav; Ozge Sonmezler; Sevcan Tug Bozdogan. 2019. "BRCAmutation characteristics in a series of index cases of breast cancer selected independent of family history." The Breast Journal 25, no. 5: 1029-1033.