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Öğe Analysis of the GCK gene in 79 MODY type 2 patients: A multicenter Turkish study, mutation profile and description of twenty novel mutations(Elsevier Science Bv, 2018) Aykut, Ayca; Karaca, Emin; Onay, Huseyin; Goksen, Damla; Cetinkalp, Sevki; Eren, Erdal; Ersoy, Betul; Cakir, Esra Papatya; Buyukinan, Muammer; Kara, Cengiz; Anik, Ahmet; Kirel, Birgul; Ozen, Samim; Atik, Tahir; Darcan, Sukran; Özkınay, FerdaMaturity onset diabetes is a genetic form of diabetes mellitus characterized by an early age at onset and several etiologic genes for this form of diabetes have been identified in many patients. Maturity onset diabetes type 2 [MODY2 (#125851)] caused by mutations in the glucokinase gene (GCK). Although its prevalence is not clear, it is estimated that 1%-2% of patients with diabetes have the monogenic form. The aim of this study was to evaluate the molecular spectrum of GCK gene mutations in 177 Turkish MODY type 2 patients. Mutations in the GCK gene were identified in 79 out of 177. All mutant alleles were identified, including 45 different GCK mutations, 20 of which were novel.Öğe Aromatase Deficiency in Two Siblings with 46,XX Karyotype Raised as Different Genders: A Novel Mutation (p.R115X) in the CYP19A1 Gene(2020) Özen, Samim; Atik, Tahir; Dilmen, Özlem Korkmaz; Onay, Hüseyin; Gökşen, Damla; Özkınay, F. Ferda; Darcan, ŞükranAromatase deficiency rarely causes a 46,XX sexual differentiation disorder. The CYP19A1 gene encodes the aromatase enzyme which catalyses the conversion of androgens to oestrogens. In cases with 46,XX karyotype, mutations in the CYP19A1 gene can lead to disorders of sex development. Clinical findings in aromatase deficiency vary depending on the degree of deficiency. The effect of increased androgens, including acne, cliteromegaly and hirsutism, can be observed in mothers with placental aromatase deficiency. A decrease in maternal virilisation symptoms is observable in the postpartum period. It is rarely reported that there is no virilization in pregnancy. In this study, two 46,XX sibling having the p.R115X (c.343 C>T) novel pathogenic variant in the CYP19A1 gene and raised as different genders, with no maternal virilisation during pregnancy, are presented. In conclusion, 46,XX virilised females should be examined in terms of aromatase deficiency once congenital adrenal hyperplasia has been excluded, even if there is no history of maternal virilisation during pregnancy.Öğe Aromatase Deficiency in Two Siblings with 46,XX Karyotype Raised as Different Genders: A Novel Mutation (p.R115X) in the CYP19A1 Gene(2020) Özen, Samim; Atik, Tahir; Dilmen, Özlem Korkmaz; Onay, Hüseyin; Gökşen, Damla; Özkınay, Ferda; Darcan, ŞükranAromatase deficiency rarely causes a 46,XX sexual differentiation disorder. the CYP19A1 gene encodes the aromatase enzyme which catalyses the conversion of androgens to oestrogens. in cases with 46,XX karyotype, mutations in the CYP19A1 gene can lead to disorders of sex development. Clinical findings in aromatase deficiency vary depending on the degree of deficiency. the effect of increased androgens, including acne, cliteromegaly and hirsutism, can be observed in mothers with placental aromatase deficiency. A decrease in maternal virilisation symptoms is observable in the postpartum period. It is rarely reported that there is no virilization in pregnancy. in this study, two 46,XX sibling having the p.R115X (c.343 C>T) novel pathogenic variant in the CYP19A1 gene and raised as different genders, with no maternal virilisation during pregnancy, are presented. in conclusion, 46,XX virilised females should be examined in terms of aromatase deficiency once congenital adrenal hyperplasia has been excluded, even if there is no history of maternal virilisation during pregnancy.Öğe Atipik Teratoid Rabdoid Tümörlü Olgularda Demografik,Klinik, Patolojik Özelliklerin ve HSNF5 (SMARCB1)/INI1Gen Mutasyonlarının Araştırılması(2020) Atik, Tahir; Ozkınay, Ferda; Işık, Esra; Kıymet, Elif; Akgün, Bilcağ; Akalın, Taner; Çetingül, NazanAmaç: Atipik teratoid/rabdoid tümör (AT/RT), çocukluk çağı santral sinir sistemi (SSS) tümörlerinden olan embriyonel tümörlerin nadir bir alt grubunu oluşturmaktadır. 22q11.2'de lokalize SMARCB1/INI1 geninde somatik dokularda oluşan değişikliklerin (delesyon, nokta mutasyonu, heterozigosite kaybı), AT/RT’lerin yaklaşık %75-98’inde bulunduğu gösterilmiştir. Ayrıca AT/RT’li hastaların 1/3’ünde SMARCB1/INI1 geninde germline mutasyonlar bildirilmiştir. Bu çalışmada, AT/RT tanısı alan hastalarda bu tümör ile ilişkili bir tümör supresör gen olan SMARCB1/INI1 mutasyonlarının araştırılması amaçlanmıştır. Gereç ve Yöntemler: Bu çalışmada, 2010-2015 yılları arasında Ege Üniversitesi Tıp Fakültesinde, AT/RT tanısı almış olguların demografik, klinik, patolojik özellikleri ve SMARCB1/INI1 mutasyonları değerlendirildi. Olguların hepsinin tümör dokusuna ait patoloji preparatlarından ve ulaşılabilen olguların periferik kanlarından DNA izole edilerek, SMARCB1/INI1 geni için tüm ekzonik bölgeler polimeraz zincir reaksiyonu ile çoğaltıldı, jel elektroforezi ile kontrol edildikten sonra DNA dizi analizi gerçekleştirildi. Tespit edilen varyasyonların patojenitesi, Amerikan Tıbbi Genetik Koleji 2015 kriterlerine göre değerlendirildi. Bulgular: Çalışmaya alınan 10 hastanın 7’si SSS’nin AT/RT’si, 2’si yumuşak dokuda RT, biri renal RT tanılıydı. Hastaların %77’sinde tümör dokusunda immünohistokimyasal yöntemler ile SMARCB1/INI1 protein ekspresyonu kaybı saptandı ve bu hastaların ortanca sağkalım süresinin 5 ay (1-69 ay, SE: 9,29 ay) olduğu görüldü. Dört hastanın tümör dokusunda SMARCB1/INI1 geninde, mutasyon saptandı ve bu hastaların ortanca sağkalım süresi 5,5 ay (1-15 ay, SE: 2,95 ay) olarak saptandı. SMARCB1/INI1 geninde mutasyon saptanmayan hastaların ortanca sağkalım süresi 10,5 ay (1-81 ay, SE: 14,6 ay) olarak saptandı. Sonuç: Tümör dokusunda SMARCB1/INI1 geninde mutasyon saptanan hastaların ortanca sağkalım sürelerinin, mutasyon saptanmayanlara göre daha kısa olduğu gözlenmiştir. Önceki yayınlardan farklı olarak AT/RT tanılı hasta grubumuzda, hiçbir hastada SMARCB1/INI1 geninde germline mutasyon saptanmamıştır.Öğe Bardet Biedl sendromlu hastalarda moleküler analiz ile fenotip-genotip korelasyonu(Ege Üniversitesi, 2014) Ece Solmaz, Aslı; Atik, Tahir; Onay, Hüseyin; Özkınay, FerdaBardet Biedl Sendromu (BBS) obezite, rod-kon distrofi, post aksiyal polidaktili, renal anomali, genital anomali ve öğrenme güçlüğü ile karakterize nadir görülen otozomal resesif geçişli bir silyopatidir. BBS'nin sıklığı toplumlar arası farklılık göstermektedir. KuzeyAvrupa'da 160.000'de 1 iken, akrabağa evliliğinin daha sık olduğu bazı Arap toplumlarında 13.500'de 1 görülmektedir. Türkiye'deki sıklığı ise bilinmemektedir. Bugüne kadar belirlenmiş BBS'den sorumlu olan 18 gen mevcuttur; BBS1, BBS2, BBS3 (ARL6), BBS4, BBS5, BBS6 (MKKS), BBS7, BBS8 (TTC8), BBS9, BBS10, BBS11 (TRIM32), BBS12, BBS13 (MKS1), BBS14 (NPHP6), BBS15 (WDPCP), BBS16 (SDCCAG8), BBS17 (LZTFL1), BBS18 (BBIP1). Bu çalışmada klinik olarak BBS tanısı konulan 15 olguda, hedeflenmiş yeni nesil dizi analizi ile 16 BBS geninde mutasyon dağılımı ve fenotip-genotip korelasyonu araştırılmıştır. Çalışmaya alınan 15 olgunun 13'ünde, araştınlan genlerde hastalığa sebep olan mutasyon saptandı. BBS1 geninde, tanımlı (Y284SfsX5), 2'si yeni (IVS1-3C>G, Q338X) 3 mutasyon, BBS2 geninde 1 yeni mutasyon (G88AfsX6), BBS4 geninde 1 yeni mutasyon (IVS6-2A>G), BBS7 geninde 1 'i tanımlı (R238EfsX59), 1 'i yeni (L317V) 2 mutasyon, BBS9 geninde 1 yeni mutasyon (N35X), BBS10 geninde 1 'i tanımlı (S311A), 3'ü yeni (K619IfsX10, 1342NfsX20, T516NfsX8) 4 mutasyon saptanmıştır. Olgular klinik bulguları ve moleküler genetik özellikleri ile fenotip-genotip korelasyonu açısından değerlendirilmiştir. Bu çalışma, BBS moleküler tanısı ve fenotip-genotip korelasyonu ile ilgili Türkiye'de ilk ve dünya literatründeki az sayıda çalışmalardan biridir. Olgulardaki moleküler bozukluğun ortaya konması, gelişebilecek komplikasyonların önlenebilmesine ve sağlıklı nesillerin yetişmesine katkı sağlayacaktır.;Bardet Biedl Sendromu, Yeni Nesil Dizi Analizi, Mutasyon, Fenotip-Genotip KorelasyonuÖğe Biallelic TOR1A mutations cause severe arthrogryposis: A case requiring reverse phenotyping(Elsevier, 2019) Isik, Esra; Aykut, Ayca; Atik, Tahir; Cogulu, Ozgur; Özkınay, FerdaHeterozygous mutations in TOR1A gene are known to be responsible for DYT1 dystonia with incomplete penetrance. Autosomal recessive TOR1A disease is a very recently described syndrome characterized by severe arthrogryposis, developmental delay, strabismus and tremor. A 2 month-old boy with severe arthrogryposis and developmental delay was referred to our department for genetic counseling. Dystonic movements were observed on physical examination. Whole exome sequencing revealed a homozygous nonsense variant in exon 5 of TOR1A (c.862C > T, p.Arg288*). Our results expand the phenotypic and mutational spectrum of biallelic TOR1A disease, while emphasizing the importance of reverse phenotyping in the diagnosis of rare genetic disorders.Öğe C20orf24: A potential novel gene responsible for Cerebrofaciothoracic Dysplasia(Elsevier, 2022) Isik, Esra; Emecen, Durdugul Ayyildiz; Atik, Tahir; Cogulu, Ozgur; Ozkinay, Ferda[No Abstract Available]Öğe C20orf24: a potential novel gene responsible for Cerebrofaciothoracic Dysplasia [2](Springernature, 2023) Isik, Esra; Emecen, Durdugul Ayyildiz; Atik, Tahir; Çoğulu, Özgür; Ozkinay, Ferda[No abstract available]Öğe A case of familial partial lipodystrophy caused by a novel lamin A/C (LMNA)mutation in exon 1 (D47N)(Elsevier Science Bv, 2016) Kutbay, Nilufer Ozdemir; Yurekli, Banu Sarer; Onay, Huseyin; Altay, Canan Tuncer; Atik, Tahir; Hekimsoy, Zeliha; Saygili, Fusun; Akinci, BarisBackground: Familial partial lipodystrophy (FPL) is a rare genetic disorder characterized by selective lack of subcutaneous fat which is associated with insulin resistant diabetes. The Dunnigan variety (FPL2) is caused by several missense mutations in the lamin A/C (LMNA) gene, most of which are typically located in exon 8 at the codon position 482. Case report: Here, we report on a Turkish family with FPL2 which is caused by a novel heterozygous missense LMNA mutation in exon 1 (D47N, c. 139G N A), in the rod domain of lamins A/C. Fat distribution and metabolic features of LMNA D47N mutation were similar to typical codon 482 mutation. Metabolic abnormalities were observed as a form of insulin resistant diabetes, hypertriglyceridemia, low HDL cholesterol and hepatic steatosis. There was no evidence for neuromuscular and cardiac involvement. Conclusion: Although it is previously known that alterations in the rod domain of type A lamins are involved in cardiac and neuromuscular diseases, our current observation shows that exon 1 LMNA mutationsmay be associated with partial lipodystrophy without any cardiac and neurological abnormalities, at least at the time of the presentation. (C) 2015 European Federation of Internal Medicine. Published by Elsevier B. V. All rights reserved.Öğe A case of gender developmental disorder with difficulty in molecular diagnosis: new variant in NR5A1 gene(Karger, 2021) Arslan, Emrullah; Solmaz, Asli Ece; Aykut, Ayca; Durmaz, Asude; Atik, Tahir; Goksen, Damla; Ulman, Ibrahim[No Abstract Available]Öğe Clinical and genetic features of L1 syndrome patients: Definition of two novel mutations(Elsevier Science Bv, 2018) Isik, Esra; Onay, Huseyin; Atik, Tahir; Akgun, Bilcag; Cogulu, Ozgur; Özkınay, FerdaL1 syndrome is a rare X linked recessive disorder caused bygene mutations in the L1 cell adhesion molecule (L1CAM), and characterized by hydrocephalus, intellectual disability, adducted thumbs and spasticity of the legs. The gene encodes a protein which plays an important role in neuronal development. Two unrelated L1 syndrome cases, with global developmental delay and hydrocephalus, were referred to pediatric genetics subdivision for genetic counseling. Bilateral adducted thumbs and spasticity in the lower extremities were also observed in both patients. Molecular analysis revealed two novel hemizygous mutations in the patients: a deletion mutation (c.749delG; p.Ser250Thrfs*51) and a splicing mutation (c.3166 + 1G > A). To conclude; in male patients with intellectual disability and hydrocephalus, where adducted thumbs are present, L1 syndrome should be considered.Öğe Clinical and molecular aspects of PTEN mutations in 10 pediatric patients(Wiley, 2020) Isik, Esra; Simsir, Ozguc Semih; Solmaz, Asli Ece; Onay, Huseyin; Atik, Tahir; Aykut, Ayca; Özkınay, FerdaIntroduction PTEN gene mutations are responsible for the PTEN hamartoma tumor syndrome (PHTS). in this study, clinical and molecular findings of patients carrying PTEN mutations are presented. Our aim is to contribute to genotype-phenotype correlation and define the most common findings of the syndrome in pediatric patients. Methods and Materials Ten molecularly confirmed PHTS patients from seven families were included in the study. All patients were examined by a clinical geneticist. Laboratory test results were obtained from hospital records. Sequencing of PTEN gene was performed. Variant interpretation was done in accordance with 2015 recommendations from the American College of Medical Genetics. Results Macrocephaly was the most common clinical finding, involving all patients. This was followed by skin lesions, neurodevelopmental delay, and pathologic cranial magnetic resonance imaging findings. Seven different heterozygous PTEN gene variants were found in seven families. Four of these were located in exon 5, which has been described as a hot spot area for the PTEN gene. Four mutations were novel. A wide range of phenotypic and genotypic spectra was found in our study group. Conclusion Screening of PTEN mutations in patients with macrocephaly is recommended due to an increased risk of cancer. Further cases are needed to make a phenotype-genotype correlation in PHTS.Öğe Clinical and molecular findings in children and young adults with persistent low alkaline phosphatase concentrations(Sage Publications Inc, 2021) Araci, Mehmet Bilal; Akgun, Bilcag; Atik, Tahir; Isik, Esra; Gunes, Ak; Barutcuoglu, Burcu; Ozkinay, FerdaBackground Hypophosphatasia is a rare inherited metabolic disease resulted by ALPL gene mutations. It is characterized by defective bone and teeth mineralization. The phenotypic spectrum is highly variable ranging from lethal perinatal form to mild forms which are only diagnosed in adulthood or remain undiagnosed despite persistently low concentrations of ALP. The aim of this study is to evaluate the clinical phenotype and frequency of ALPL mutations in a group of patient with hypophosphatasaemia. Methods Thirty individuals with alkaline phosphatase values below 40 IU/L in at least two assessments and having no alternative explanation for their low ALP concentrations were included in the study. The clinical features and radiological data of the study group were re-investigated for hypophosphatasia-related findings. ALPL sequence analysis was performed using Sanger sequencing. Results No patient in the study group had severe symptoms, nor had they initially been diagnosed as having hypophosphatasia. Four different heterozygous ALPL mutations (c.542C>T, c.648 + 1G>A, c.657G>T and c.862 + 1G>C) were found in four patients. One splice site mutation (c.862 + 1G>C) was reported for the first time in this study. Conclusion ALPL sequence analysis may help to diagnosing genetic defects in individuals with persistently low ALP concentrations and provide to take preventive measures before symptoms appear. As in the other populations, HPP displays allelic heterogeneity in our population.Öğe Clinical and Molecular Spectrum of Four Patients Diagnosed with Mowat-Wilson Syndrome(Karger, 2020) Ayyildiz Emecen, Durdugul; Isik, Esra; Utine, Gulen E.; Simsek-Kiper, Pelin O.; Atik, Tahir; Ozkinay, FerdaMowat-Wilson syndrome (MWS) is a rare autosomal dominant syndrome characterized by distinctive facial features, congenital heart defects, Hirschsprung disease, genitourinary anomalies, various structural brain anomalies, and intellectual disability. Pathogenic mutations that result in haploinsufficiency in the ZEB2 gene cause MWS. in this study, we aimed to evaluate the clinical features and molecular analysis results of 4 MWS patients. All patients were examined by an expert clinical geneticist. Dysmorphological abnormalities were recorded. Data including demographic, clinical, and laboratory findings were obtained from hospital records. ZEB2 gene analysis was performed using a Sanger sequencing method. All patients had typical facial features of MWS such as widely spaced eyes, broad eyebrows with a medial flare, low-hanging columella, prominent or pointed chin, open-mouth expression, and uplifted earlobes. Four different heterozygous mutations were identified; 2 mutations were frameshift (c.246_247delGGinsC, c.980_980delG), 1 was nonsense (c.2083C>T), and 1 was splice site (c.808-2A>G). Two of them (c.246_247delGGinsC, c.980_980delG) have not been previously reported in the literature. By defining 2 novel mutations, this study contributes to the molecular spectrum of MWS, while also providing a further insight for genetic counseling. It also demonstrates the importance of dysmorphological examination in clinical diagnosis.Öğe Clinical and Molecular Spectrum of Tuberous Sclerosis Complex Patients: Identification of Three Novel Mutations(Erciyes Univ Sch Medicine, 2021) Isik, Esra; Onay, Huseyin; Atik, Tahir; Solmaz, Ash Ece; Terek, Demet; Gokben, Sarenur; Cogulu, OzgurObjective: Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome. TSC arises from mutations in either TSC1, at 9q34, or TSC2, at 16p13.3. Skin lesions, such as hypomelanotic macules, facial angiofibromas, shagreen patches, and ungual fibromas, are frequently seen in these patients. The present study aims to investigate clinical manifestations, molecular findings and phenotype-genotype correlations in 17 patients with TSC. Materials and Methods: TSC1 and TSC2 molecular analyses were performed on a next-generation sequencing platform (Illumina MiSeq). Variant interpretation was made in accordance with the American College of Medical Genetics 2015 recommendations. Results: Four patients carried a heterozygous mutation in TSC1, while the remaining seven carried mutations in TSC2. Three novel variants in TSC2 were defined. Sequencing failed to detect a mutation in six patients. in only one of these patients, multiplex ligation-dependent probe amplification (MLPA (R)) could be performed, and a large deletion in the TSC1 gene was detected. A wide spectrum of phenotypic features was noted throughout the study group. Dermatological findings were observed in almost all patients. Conclusion: in this study, in addition to the three novel mutations reported herein, the spectrum of TSC1 and TSC2 gene mutations and their phenotypes were reported.Öğe Clinical and Molecular Spectrum of TuberousSclerosis Complex Patients: Identification of ThreeNovel Mutations(2021) Işık, Esra; Tekgül, Hasan; Kantar, Mehmet; Çoğullu, Özgür; Atik, Tahir; Solmaz, Aslı Ece; Terek, DemetObjective: Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome. TSC arises from mu tations in either TSC1, at 9q34, or TSC2, at 16p13.3. Skin lesions, such as hypomelanotic macules, facial angiofibromas,shagreen patches, and ungual fibromas, are frequently seen in these patients. The present study aims to investigate clinicalmanifestations, molecular findings and phenotype-genotype correlations in 17 patients with TSC. Materials and Methods: TSC1 and TSC2 molecular analyses were performed on a next-generation sequencing platform(Illumina MiSeq). Variant interpretation was made in accordance with the American College of Medical Genetics 2015 rec ommendations. Results: Four patients carried a heterozygous mutation in TSC1, while the remaining seven carried mutations in TSC2.Three novel variants in TSC2 were defined. Sequencing failed to detect a mutation in six patients. In only one of these pa tients, multiplex ligation-dependent probe amplification (MLPA®) could be performed, and a large deletion in the TSC1 genewas detected. A wide spectrum of phenotypic features was noted throughout the study group. Dermatological findings wereobserved in almost all patients. Conclusion: In this study, in addition to the three novel mutations reported herein, the spectrum of TSC1 and TSC2 genemutations and their phenotypes were reported.Öğe Clinical presentations, metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy(W B Saunders Co-Elsevier Inc, 2017) Akinci, Baris; Onay, Huseyin; Demir, Tevfik; Savas-Erdeve, Senay; Gen, Ramazan; Simsir, Ilgin Yildirim; Keskin, Fatma Ela; Erturk, Mehmet Sercan; Uzum, Ayse Kubat; Yaylali, Guzin Fidan; Ozdemir, Nilufer Kutbay; Atik, Tahir; Ozen, Samim; Yurekli, Banu Sarer; Apaydin, Tugce; Altay, Canan; Akinci, Gulcin; Demir, Leyla; Comlekci, Abdurrahman; Secil, Mustafa; Oral, Elif AriogluObjective. Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by partial lack of subcutaneous fat. Methods. This multicenter prospective observational study included data from 56 subjects with FPLD (18 independent Turkish families). Thirty healthy controls were enrolled for comparison. Results. Pathogenic variants of the LMNA gene were determined in nine families. Of those, typical exon 8 codon 482 pathogenic variants were identified in four families. Analysis of the LMNA gene also revealed exon 1 codon 47, exon 5 codon 306, exon 6 codon 349, exon 9 codon 528, and exon 11 codon 582 pathogenic variants. Analysis of the PPARG gene revealed exon 3 p.Y151C pathogenic variant in two families and exon 7 p.H477L pathogenic variant in one family. A non-pathogenic exon 5 p.R215Qvariant of the LMNB2 gene was detected in another family. Five other families harbored no mutation in any of the genes sequenced. MRI studies showed slightly different fat distribution patterns among subjects with different point mutations, though it was strikingly different in subjects with LMNA p.R349W pathogenic variant. Subjects with pathogenic variants of the PPARG gene were associated with less prominent fat loss and relatively higher levels of leptin compared to those with pathogenic variants in the LMNA gene. Various metabolic abnormalities associated with insulin resistance were detected in all subjects. End-organ complications were observed. Conclusion. We have identified various pathogenic variants scattered throughout the LMNA and PPARG genes in Turkish patients with FPLD. Phenotypic heterogeneity is remarkable in patients with LMNA pathogenic variants related to the site of missense mutations. FPLD, caused by pathogenic variants either in LMNA or PPARG is associated with metabolic abnormalities associated with insulin resistance that lead to increased morbidity. (C) 2017 Elsevier Inc. All rights reserved.Öğe Clinical utility of a targeted next generation sequencing panel in severe and pediatric onset Mendelian diseases(Elsevier, 2019) Isik, Esra; Onay, Huseyin; Atik, Tahir; Canda, Ebru; Cogulu, Ozgur; Coker, Mahmut; Özkınay, FerdaNext generation sequencing has provided great advancements in genetic diagnosis of Mendalian disorders. Simultaneous sequencing of many genes has become increasingly cheaper and faster. Recently, a number of gene panels have been established for the diagnosis of specific disease groups. The aim of this study is to evaluate the utility of an inherited disease panel in pediatric onset Mendelian diseases. Two hundred and seventeen probands and 10 carriers molecularly analyzed using a TruSight Inherited Disease Panel which included 552 genes responsible for pediatric onset Mendelian disorders, were enrolled in the study. The clinical phenotype, sequencing data, pretest and posttest diagnoses were evaluated. The patients in the study were classified into two groups. Group 1 (n:209) included the patients having a clinical diagnosis prior to molecular analysis. Group 2 (n:18) included the patients undiagnosed clinically prior to molecular analysis. Targeted panel provided a molecular diagnosis in 37% (84 of 227 cases) of all cases. The molecular diagnostic rate was 40.2% in patients with a specific prior clinical diagnosis. However, in patients having no primary clinical diagnosis no pathogenic variants were found. In 14 patients, a molecular diagnosis differing from the established clinical diagnosis was made. In conclusion, a targeted panel covering a high number of genes responsible for broad phenotypic spectrum can provide improved levels of diagnosis in patients with pediatric onset Mendelian diseases. A careful clinical evaluation of patients prior to the application of a next generation sequencing method leads to the best alternative approach for a conclusive molecular diagnosis.Öğe Comprehensive Analysis of Deafness Genes in Families with Autosomal Recessive Nonsyndromic Hearing Loss(Public Library Science, 2015) Atik, Tahir; Onay, Huseyin; Aykut, Ayca; Bademci, Guney; Kirazli, Tayfun; Tekin, Mustafa; Özkınay, FerdaComprehensive genetic testing has the potential to become the standard of care for individuals with hearing loss. In this study, we investigated the genetic etiology of autosomal recessive nonsyndromic hearing loss (ARNSHL) in a Turkish cohort including individuals with cochlear implant, who had a pedigree suggestive of an autosomal recessive inheritance. A workflow including prescreening of GJB2 and a targeted next generation sequencing panel (Illumina TruSight (TM) Exome) covering 2761 genes that we briefly called as mendelian exome sequencing was used. This panel includes 102 deafness genes and a number of genes causing Mendelian disorders. Using this approach, we identified causative variants in 21 of 29 families. Three different GJB2 variants were present in seven families. Remaining 14 families had 15 different variants in other known NSHL genes (MYO7A, MYO15A, MARVELD2, TMIE, DFNB31, LOXHD1, GPSM2, TMC1, USH1G, CDH23). Of these variants, eight are novel. Mutation detection rate of our workflow is 72.4%, confirming the usefulness of targeted sequencing approach in NSHL.Öğe Detection of Copy Number Variations by Microarray in Disorders of Sex Development of Unexplained Molecular Etiology and Association with Clinical Findings(Karger, 2022) Karatas, Murat Caglar; Evin, Ferda; Atik, Tahir; Ata, Aysun; Er, Eren; Goksen, Damla; Darcan, Sukran[No Abstract Available]