Browsing by Author "Yildiz N."

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    Prevalence of Childhood Affective disorders in Turkey: An epidemiological study
    (Elsevier B.V., 2018) Karacetin G.; Arman A.R.; Fis N.P.; Demirci E.; Ozmen S.; Hesapcioglu S.T.; Oztop D.; Tufan A.E.; Tural U.; Aktepe E.; Aksu H.; Ardic U.A.; Basgul S.; Bilac O.; Coskun M.; Celik G.G.; Demirkaya S.K.; Dursun O.B.; Durukan I.; Fidan T.; Gencoglan S.; Gokcen C.; Gokten E.S.; Gorker I.; Gormez V.; Gundogdu O.Y.; Gurkan C.K.; Herguner S.; Kandemir H.; Kilic B.G.; Kilincaslan A.; Mutluer T.; Nasiroglu S.; Ozcan O.O.; Ozturk M.; Sapmaz S.Y.; Suren S.; Sahin N.; Tahiroglu A.Y.; Toros F.; Unal F.; Vural P.; Yazici I.P.; Yazici K.U.; Yildirim V.; Yulaf Y.; Yuce M.; Yuksel T.; Akdemir D.; Altun H.; Ayik B.; Bilgic A.; Bozkurt O.H.; Cakir E.D.; Ceri V.; Demir N.U.; Dinc G.; Irmak M.Y.; Karaman D.; Kinik M.F.; Mazlum B.; Memik N.C.; Ozdemir D.F.; Sinir H.; Tasdelen B.I.; Taskin B.; Ugur C.; Uran P.; Uysal T.; Uneri O.S.; Yilmaz S.; Yilmaz S.S.; Acikel B.; Aktas H.; Alaca R.; Alic B.G.; Almbaidheen M.; Ari F.P.; Aslan C.; Atabay E.; Ay M.G.; Aydemir H.; Ayranci G.; Babadagi Z.; Bayar H.; Bayhan P.C.; Bayram O.; Bektas N.D.; Berberoglu K.K.; Bostan R.; Cakan Y.; Canli M.A.; Cansiz M.A.; Ceylan C.; Coskun N.; Coskun S.; Demir I.; Demir N.; Demirdogen E.Y.; Dogan B.; Donmez Y.E.; Donder F.; Efe A.; Eray S.; Erbilgin S.; Erden S.; Ersoy E.G.; Eseroglu T.; Firat S.K.; Gok E.E.; Goksoy S.C.; Guler G.; Gules Z.; Gunay G.; Gunes S.; Gunes A.; Guven G.; Horozcu H.; Irmak A.; Isik U.; Kahraman O.; Kalayci B.M.; Karaaslan U.; Karadag M.; Kilic H.T.; Kilicaslan F.; Kinay D.; Koc E.B.; Kocael O.; Mutlu R.K.; San Z.; Nalbant K.; Okumus N.; Ozbek F.; Ozdemir F.A.; Ozdemir H.; Ozgur B.G.; Ozkan S.; Ozyurt E.Y.; Polat B.; Polat H.; Sekmen E.; Sertcelik M.; Sevgen F.H.; Sevince O.; Shamkhalova U.; Suleyman F.; Simsek N.E.; Tanir Y.; Tekden M.; Temtek S.; Topal M.; Topal Z.; Turk T.; Ucar H.N.; Ucar F.; Uygun D.; Uzun N.; Vatansever Z.; Yazgili N.G.; Yildiz D.M.; Yildiz N.; Ercan E.S.
    Aim: To determine the prevalence of affective disorders in Turkey among a representative sample of Turkish population. Methods: This study was conducted as a part of the “The Epidemiology of Childhood Psychopathology in Turkey” (EPICPAT-T) Study, which was designed by the Turkish Association of Child and Adolescent Mental Health. The inclusion criterion was being a student between the second and fourth grades in the schools assigned as study centers. The assessment tools used were the K-SADS-PL, and a sociodemographic form that was designed by the authors. Impairment was assessed via a 3 point-Likert type scale independently rated by a parent and a teacher. Results: A total of 5842 participants were included in the analyses. The prevalence of affective disorders was 2.5 % without considering impairment and 1.6 % when impairment was taken into account. In our sample, the diagnosis of bipolar disorder was lacking, thus depressive disorders constituted all the cases. Among depressive disorders with impairment, major depressive disorder (MDD) (prevalence of 1.06%) was the most common, followed by dysthymia (prevalence of 0.2%), adjustment disorder with depressive features (prevalence of 0.17%), and depressive disorder-NOS (prevalence of 0.14%). There were no statistically significant gender differences for depression. Maternal psychopathology and paternal physical illness were predictors of affective disorders with pervasive impairment. Conclusion: MDD was the most common depressive disorder among Turkish children in this nationwide epidemiological study. This highlights the severe nature of depression and the importance of early interventions. Populations with maternal psychopathology and paternal physical illness may be the most appropriate targets for interventions to prevent and treat depression in children and adolescents. © 2018
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    Shared Biological Pathways and Processes in Patients with Intellectual Disability: A Multicenter Study
    (Georg Thieme Verlag, 2022) Günay Ç.; Aykol D.; Özsoy Ö.; Sönmezler E.; Hanci Y.S.; Kara B.; Akkoyunlu Sünnetçi D.; Cine N.; Deniz A.; Özer T.; Ölçülü C.B.; Yilmaz Ö.; Kanmaz S.; Yilmaz S.; Tekgül H.; Yildiz N.; Acar Arslan E.; Cansu A.; Olgaç Dündar N.; Kusgoz F.; Didinmez E.; Gençpinar P.; Aksu Uzunhan T.; Ertürk B.; Gezdirici A.; Ayaz A.; Ölmez A.; Ayanoǧlu M.; Tosun A.; Topçu Y.; Kiliç B.; Aydin K.; Çaǧlar E.; Ersoy Kosvali Ö.; Okuyaz Ç.; Besen Ş.; Tekin Orgun L.; Erol İ.; Yüksel D.; Sezer A.; Atasoy E.; Toprak Ü.; Güngör S.; Ozgor B.; Karadaǧ M.; Dilber C.; Şahinoǧlu B.; Uyur Yalçin E.; Eldes Hacifazlioglu N.; Yaramiś A.; Edem P.; Gezici Tekin H.; Yilmaz Ü.; Ünalp A.; Turay S.; Biçer D.; Gül Mert G.; Dokurel Çetin İ.; Kirik S.; Öztürk G.; Karal Y.; Sanri A.; Aksoy A.; Polat M.; Özgün N.; Soydemir D.; Sarikaya Uzan G.; Ülker Üstebay D.; Gök A.; Yeśilmen M.C.; Yiś U.; Karakülah G.; Bursali A.; Oktay Y.; Hiz Kurul S.
    Background  Although the underlying genetic causes of intellectual disability (ID) continue to be rapidly identified, the biological pathways and processes that could be targets for a potential molecular therapy are not yet known. This study aimed to identify ID-related shared pathways and processes utilizing enrichment analyses. Methods  In this multicenter study, causative genes of patients with ID were used as input for Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Results  Genetic test results of 720 patients from 27 centers were obtained. Patients with chromosomal deletion/duplication, non-ID genes, novel genes, and results with changes in more than one gene were excluded. A total of 558 patients with 341 different causative genes were included in the study. Pathway-based enrichment analysis of the ID-related genes via ClusterProfiler revealed 18 shared pathways, with lysine degradation and nicotine addiction being the most common. The most common of the 25 overrepresented DO terms was ID. The most frequently overrepresented GO biological process, cellular component, and molecular function terms were regulation of membrane potential, ion channel complex, and voltage-gated ion channel activity/voltage-gated channel activity, respectively. Conclusion  Lysine degradation, nicotine addiction, and thyroid hormone signaling pathways are well-suited to be research areas for the discovery of new targeted therapies in ID patients. © 2022 Hippokrates Verlag GmbH. All rights reserved.
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    COVID-19 in pediatric nephrology centers in Turkey
    (Turkiye Klinikleri, 2022) Leventoğlu E.; Atikel Y.Ö.; Nalçacioğlu H.; Dursun I.; Dursun H.; Yildirim Z.Y.; Yildiz N.; Aksoy G.K.; Taşdemir M.; Çelakil M.; Kiliç B.D.; Selçuk Ş.Z.; Canpolat N.; Çakici E.K.; Özlü S.G.; Tülpar S.; Yüksel S.; Atmiş B.; Döven S.S.; Taner S.; Ertan P.; Kavaz A.; Bayram M.T.; Kalyoncu M.; Gülleroğlu K.; Kabasakal C.; Demir B.K.; Çiçek R.Y.; Bilge I.; Dönmez O.; Kara A.; Yavaşcan Ö.; Özçelik G.; Yildirim D.G.; Güler M.A.; Sönmez F.; Poyrazoğlu H.; Akman S.; Topaloğlu R.; Alpay H.; Bakkaloğlu S.A.
    Background/aim: There is limited data on COVID-19 disease in children with kidney disease. We aimed to investigate the characteristics and prognosis of COVID-19 in pediatric nephrology patients in Turkey. Materials and methods: This was a national, multicenter, retrospective cohort study based on an online survey evaluating the data between 11th March 2020 and 11th March 2021 as an initial step of a detailed pediatric nephrology COVID-19 registry. Results: Two hundred and three patients (89 girls and 114 boys) were diagnosed with COVID-19. One-third of these patients (36.9%) were between 10–15 years old. Half of the patients were on kidney replacement therapy: kidney transplant (KTx) recipients (n = 56, 27.5%), patients receiving chronic hemodialysis (n = 33, 16.3%) and those on peritoneal dialysis (PD) (n = 18, 8.9%). Fifty-four (26.6%) children were asymptomatic. Eighty-two (40.3%) patients were hospitalized and 23 (28%) needed intensive care unit admission. Fifty-five percent of the patients were not treated, while the remaining was given favipiravir (20.7%), steroid (16.3%), and hydroxychloroquine (11.3%). Acute kidney injury developed in 19.5% of hospitalized patients. Five (2.4%) had MIS-C. Eighty-three percent of the patients were discharged without any apparent sequelae, while 7 (3.4%) died. One hundred and eight health care staff were infected during the study period. Conclusion: COVID-19 was most commonly seen in patients who underwent KTx and received HD. The combined immunosuppressive therapy and frequent exposure to the hospital setting may increase these patients’ susceptibility. Staff infections before vaccination era were alarming, various precautions should be taken for infection control, particularly optimal vaccination coverage. © TÜBİTAK.
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    Kidney disease profile and encountered problems during follow-up in Syrian refugee children: a multicenter retrospective study
    (Springer Science and Business Media Deutschland GmbH, 2022) Balat A.; Kilic B.D.; Aksu B.; Kara M.A.; Buyukcelik M.; Agbas A.; Eroglu F.K.; Gungor T.; Alaygut D.; Yildiz N.; Bastug F.; Atmis B.; Melek E.; Elmaci M.; Tulpar S.; Pehlivanoglu C.; Doven S.S.; Comak E.; Tabel Y.; Gemici A.; Uysal B.; Ozzorlar G.S.; Kuçuk N.; Delibas A.; Ozcelik G.; Goknar N.; Dursun I.; Ertan P.; Ozunan I.A.; Sonmez F.
    Background: Children are one of the most vulnerable groups in conflict zones, especially those with chronic diseases. This study aimed to investigate kidney disease profiles and problems during follow-up in a population of Syrian refugee children residing in Turkey. Methods: Syrian refugee children aged between 0 and 18 years were included in the study. Demographic data, diagnosis, particular interventions due to nephrological problems, and problems encountered during follow-up were obtained from all participating pediatric nephrology centers. Results: Data from 633 children from 22 pediatric nephrology centers were included. Mean age of the children was 94.8 ± 61.7 months and 375 were male (59%). 57.7% had parental consanguinity and 23.3% had a close relative(s) with kidney disease. The most common kidney diseases were congenital anomalies of the kidney and urinary tract (CAKUT) (31.0%), glomerular disease (19.9%), chronic kidney disease (CKD) (14.8%), and urolithiasis (10.7%). Frequent reasons for CAKUT were nonobstructive hydronephrosis (23.0%), vesico-ureteral reflux (18.4%), and neurogenic bladder (15.8%). The most common etiology of glomerular diseases was nephrotic syndrome (69%). Ninety-four children had CKD, and 58 children were on chronic dialysis. Six children had kidney transplantation. Surgical intervention was performed on 111 patients. The language barrier, lack of medical records, and frequent disruptions in periodic follow-ups were the main problems noted. Conclusions: CAKUT, glomerular disease, and CKD were highly prevalent in Syrian refugee children. Knowing the frequency of chronic diseases and the problems encountered in refugees would facilitate better treatment options and preventive measures. © 2021, IPNA.
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    Comparison of immunogenicity for Sinovac-CoronaVac vaccine vs. natural infection during cancer treatment
    (Verduci Editore s.r.l, 2023) Çakir E.; Saydan D.; Gülbagci B.; Özen M.; Uǧurlu İ.; Demirci A.; Bilir F.; Hacibekiroglu İ.; Yildiz N.; Akcali S.; Altindis M.; Varim C.; Yaylaci S.; Bilir C.
    OBJECTIVE: Efficacy of the COVID-19 vaccines in cancer patients, especially during their active treatment, are lacking. Most of the studies in the literature compared the immunity in cancer patients with a cross-sectional cohort or retrospectively. Our study investigated Sinovac- CoronaVac COVID-19 vaccine immunogenicity and compared it with natural COVID-19 disease in cancer patients during their cancer therapy. PATIENTS AND METHODS: A total of 111 patients with cancer and who are on active treatment were included in the study. This is a single- center study and was designed prospectively. Two group of patients were included in the study, natural disease and vaccinated group. RESULTS: A total of 111 patients were included in the study, 34 of whom had natural COVID-19 disease. Antibody levels following the first dose vaccine were 0.4 (0-1.9) U/ml while after the second dose of vaccine were 2.6 (1.0- 7.25) U/ml. Immunogenicity levels were 82.4% in the natural disease group and 75.8% in the vaccinated group after the second shot of the vaccine. Immunogenicity rate was significantly higher in non-chemotherapy (receiving immunotehrapy/ targeted therapy or biologic agent) group compared to chemotherapy drug (92.9% vs. 63.3%, p=0.004). There was a difference between the antibody levels following the first and second vaccination [median (IQR): 0.3 (0-1.0) and 3.3 (2.0-6.7), p=0.001, respectively]. CONCLUSIONS: The present study revealed that the Sinovac-CoronaVac vaccine showed an acceptable immunogenicity following two shots in cancer patients who were receiving active systemic therapy. On the other hand, natural disease immunogenicity was higher than vaccinated group. © 2023 Verduci Editore s.r.l. All rights reserved.
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    Urinary HSP70 improves diagnostic accuracy for urinary tract infection in children: UTILISE study
    (Springer Science and Business Media Deutschland GmbH, 2023) Yilmaz A.; Afonso A.C.; Akil I.; Aksu B.; Alpay H.; Atmis B.; Aydog O.; Bayazıt A.K.; Bayram M.T.; Bilge I.; Bulut I.K.; Buyukkaragoz B.; Comak E.; Demir B.K.; Dincel N.; Donmez O.; Durmus M.A.; Dursun H.; Dusunsel R.; Duzova A.; Ertan P.; Gedikbasi A.; Goknar N.; Guven S.; Hacihamdioglu D.; Jankauskiene A.; Kalyoncu M.; Kavukcu S.; Kenan B.U.; Kucuk N.; Kural B.; Litwin M.; Montini G.; Morello W.; Nayir A.; Obrycki L.; Omer B.; Ozdemir E.M.; Ozkayin N.; Paripovic D.; Pehlivanoglu C.; Saygili S.; Schaefer S.; Sonmez F.; Tabel Y.; Tas N.; Tasdemir M.; Teixeira A.; Tekcan D.; Tulpar S.; Turkkan O.N.; Uysal B.; Uysalol M.; Vaiciuniene D.; Yavuz S.; Yel S.; Yildirim T.; Yildirim Z.Y.; Yildiz N.; Yuksel S.; Yurtseven E.; Schaefer F.; Topaloglu R.
    Background: The accuracy of conventional urinalysis in diagnosing urinary tract infection (UTI) in children is limited, leading to unnecessary antibiotic exposure in a large fraction of patients. Urinary heat shock protein 70 (uHSP70) is a novel marker of acute urinary tract inflammation. We explored the added value of uHSP70 in discriminating UTI from other infections and conditions confused with UTI. Methods: A total of 802 children from 37 pediatric centers in seven countries participated in the study. Patients diagnosed with UTI (n = 191), non-UTI infections (n = 178), contaminated urine samples (n = 50), asymptomatic bacteriuria (n = 26), and healthy controls (n = 75) were enrolled. Urine and serum levels of HSP70 were measured at presentation in all patients and after resolution of the infection in patients with confirmed UTI. Results: Urinary (u)HSP70 was selectively elevated in children with UTI as compared to all other conditions (p < 0.0001). uHSP70 predicted UTI with 89% sensitivity and 82% specificity (AUC = 0.934). Among the 265 patients with suspected UTI, the uHSP70 > 48 ng/mL criterion identified the 172 children with subsequently confirmed UTI with 90% sensitivity and 82% specificity (AUC = 0.862), exceeding the individual diagnostic accuracy of leukocyturia, nitrite, and leukocyte esterase positivity. uHSP70 had completely normalized by the end of antibiotic therapy in the UTI patients. Serum HSP70 was not predictive. Conclusions: Urine HSP70 is a novel non-invasive marker of UTI that improves the diagnostic accuracy of conventional urinalysis. We estimate that rapid urine HSP70 screening could spare empiric antibiotic administration in up to 80% of children with suspected UTI. Graphical abstract: A higher resolution version of the Graphical abstract is available as Supplementary information [Figure not available: see fulltext.] © 2022, The Author(s), under exclusive licence to International Pediatric Nephrology Association.
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    The relationship between urine heat shock protein 70 and congenital anomalies of the kidney and urinary tract: UTILISE study
    (Frontiers Media SA, 2023) Aksu B.; Afonso A.C.; Akil I.; Alpay H.; Atmis B.; Aydog O.; Bakkaloglu S.; Bayazıt A.K.; Bayram M.T.; Bilge I.; Bulut I.K.; Cetinkaya A.P.G.; Comak E.; Demir B.K.; Dincel N.; Donmez O.; Durmus M.A.; Dursun H.; Dusunsel R.; Duzova A.; Ertan P.; Gedikbasi A.; Goknar N.; Guven S.; Hacihamdioglu D.; Jankauskiene A.; Kalyoncu M.; Kavukcu S.; Kenan B.U.; Kucuk N.; Kural B.; Litwin M.; Montini G.; Morello W.; Obrycki L.; Omer B.; Misirli Ozdemir E.; Ozkayin N.; Paripovic D.; Pehlivanoglu C.; Saygili S.; Schaefer F.; Schaefer S.; Sonmez F.; Tabel Y.; Tas N.; Tasdemir M.; Teixeira A.; Tekcan D.; Topaloglu R.; Tulpar S.; Turkkan O.N.; Uysal B.; Uysalol M.; Vitkevic R.; Yavuz S.; Yel S.; Yildirim T.; Yildirim Z.Y.; Yildiz N.; Yuksel S.; Yurtseven E.; Yilmaz A.
    Background: Congenital anomalies of the kidney and urinary tract (CAKUT) are defined as structural malformations of the kidney and/or urinary tract. Heat shock proteins (HSPs) are expressed in the kidney in response to cellular changes, such as thermal, hemodynamic, osmotic, inflammatory, and mechanical stresses. This study aimed to assess uHSP70 levels during acute urinary tract infections (UTI) and non-infection periods in patients with CAKUT, and to evaluate whether uHSP70 is elevated in CAKUT subtypes. Methods: Among patients with CAKUT, 89 patients with UTI (CAKUT-A), 111 without UTI (CAKUT-B), and 74 healthy children were included in the study. uHSP70 levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: uHSP70 level was significantly higher in the CAKUT-A group than in the CAKUT-B and healthy control groups (p < 0.0001). Moreover, the level of uHSP70 was significantly higher in the CAKUT-B group than in the control group (p < 0.0001), but was not different between the CAKUT subtypes (p > 0.05). Conclusion: Urine HSP70 can also be used to predict UTI in patients with CAKUT. Moreover, uHSP70 levels were higher in children with CAKUT during the non-infectious period than in healthy controls. This suggests that children with CAKUT are at risk of chronic non-infectious damage. Copyright © 2024 Aksu, Afonso, Akil, Alpay, Atmis, Aydog, Bakkaloglu, Bayazıt, Bayram, Bilge, Bulut, Cetinkaya, Comak, Demir, Dincel, Donmez, Durmus, Dursun, Dusunsel, Duzova, Ertan, Gedikbasi, Goknar, Guven, Hacihamdioglu, Jankauskiene, Kalyoncu, Kavukcu, Kenan, Kucuk, Kural, Litwin, Montini, Morello, Obrycki, Omer, Misirli Ozdemir, Ozkayin, Paripovic, Pehlivanoglu, Saygili, Schaefer, Schaefer, Sonmez, Tabel, Tas, Tasdemir, Teixeira, Tekcan, Topaloglu, Tulpar, Turkkan, Uysal, Uysalol, Vitkevic, Yavuz, Yel, Yildirim, Yildirim, Yildiz, Yuksel, Yurtseven and Yilmaz.
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    Urine soluble TLR4 levels may contribute to predict urinary tract infection in children: the UTILISE Study
    (Springer Science and Business Media Deutschland GmbH, 2024) Aksu B.; Afonso A.C.; Akil I.; Alpay H.; Atmis B.; Aydog O.; Bayazıt A.K.; Bayram M.T.; Bilge I.; Bulut I.K.; Buyukkaragoz B.; Comak E.; Demir B.K.; Dincel N.; Donmez O.; Durmus M.A.; Dursun H.; Dusunsel R.; Duzova A.; Ertan P.; Gedikbasi A.; Goknar N.; Guven S.; Hacihamdioglu D.; Jankauskiene A.; Kalyoncu M.; Kavukcu S.; Kenan B.U.; Kucuk N.; Kural B.; Litwin M.; Montini G.; Morello W.; Obrycki L.; Omer B.; Oner H.A.; Ozdemir E.M.; Ozkayin N.; Paripovic D.; Pehlivanoglu C.; Saygili S.; Schaefer F.; Schaefer S.; Sonmez F.; Tabel Y.; Tas N.; Tasdemir M.; Teixeira A.; Tekcan D.; Topaloglu R.; Tulpar S.; Turkkan O.N.; Uysal B.; Uysalol M.; Vitkevic R.; Yavuz S.; Yel S.; Yildirim T.; Yildirim Z.Y.; Yildiz N.; Yuksel S.; Yurtseven E.; Yilmaz A.
    Background: One of the most common bacterial infections in childhood is urinary tract infection (UTI). Toll-like receptors (TLRs) contribute to immune response against UTI recognizing specific pathogenic agents. Our aim was to determine whether soluble TLR4 (sTLR4), soluble TLR5 (sTLR5) and interleukin 8 (IL-8) can be used as biomarkers to diagnose UTI. We also aimed to reveal the relationship between urine Heat Shock Protein 70 (uHSP70) and those biomarkers investigated in this study. Methods: A total of 802 children from 37 centers participated in the study. The participants (n = 282) who did not meet the inclusion criteria were excluded from the study. The remaining 520 children, including 191 patients with UTI, 178 patients with non-UTI infections, 50 children with contaminated urine samples, 26 participants with asymptomatic bacteriuria and 75 healthy controls were included in the study. Urine and serum levels of sTLR4, sTLR5 and IL-8 were measured at presentation in all patients and after antibiotic treatment in patients with UTI. Results: Urine sTLR4 was higher in the UTI group than in the other groups. UTI may be predicted using 1.28 ng/mL as cut-off for urine sTLR4 with 68% sensitivity and 65% specificity (AUC = 0.682). In the UTI group, urine sTLR4 levels were significantly higher in pyelonephritis than in cystitis (p < 0.0001). Post-treatment urine sTLR4 levels in the UTI group were significantly lower than pre-treatment values (p < 0.0001). Conclusions: Urine sTLR4 may be used as a useful biomarker in predicting UTI and subsequent pyelonephritis in children with UTI. Graphical abstract: [Figure not available: see fulltext.]. © 2023, The Author(s), under exclusive licence to International Pediatric Nephrology Association.
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    Therapeutic implications of etiology-specific diagnosis of early-onset developmental and epileptic encephalopathies (EO-DEEs): A nationwide Turkish cohort study
    (W.B. Saunders Ltd, 2024) Kanmaz S.; Tekgul H.; Kayilioglu H.; Atas Y.; Kart P.O.; Yildiz N.; Gumus H.; Aydin K.; Olculu C.B.; Dogan D.E.T.; Per H.; Canpolat M.; Gulec A.; Yildirim N.; Turk E.; Celik N.; Ozturk S.; Kumandas S.; Kilic B.; Topcu Y.; Ozpinar E.; Coskun A.; Arslan M.; Akkoyunlu D.S.; Cine N.; Uzan G.S.; Gunay C.; Akyol D.; Ersoy O.; Direk M.C.; Komur M.; Kirkgoz H.; Karaoğlu P.; Ibis I.B.P.; Cerci C.; Orak A.; Oktay S.; Ayanoglu M.; Yildirim M.; Bektas O.; Serdaroglu E.; Yilmaz S.B.; Cankurt I.; Hirfanoglu T.; Arhan E.; Gencpinar P.; Dundar N.O.; Teber S.; Serin H.M.; Yilmaz S.; Tosun A.; Polat M.; Yilmaz U.; Unalp A.; Kara B.; Okuyaz C.; Yis U.; Hiz S.; Aktan G.; Gokben S.; Unay B.; Serdaroglu A.; Cansu A.
    Objective: To evaluate the etiology-specific diagnosis of early-onset developmental epileptic encephalopathies (EO-DEEs) in a nationwide Turkish cohort to determine the implications for therapeutic management. Methods: The cohort comprised 1450 patients who underwent EO-DEE. The utility of genetic testing was assessed with respect to the initial phases of next generation sequencing (NGS) (2005–2013) and the current NGS era (2014–2022). A predefined four-stepwise diagnostic model was evaluated using cost-effectiveness analysis. The diagnostic and potential therapeutic yields of the genetic tests were subsequently determined. Results: Gene-related EO-DEEs were identified in 48.3 % (n = 701) of the cohort: non-structural genetic (62.6 %), metabolic genetic (15.1 %), and structural genetic (14.1 %). The most common nonstructural genetic variants were SCN1A (n = 132, 18.8 %), CDKL5 (n = 30, 4.2 %), STXBP1 (n = 21, 2.9 %), KCNQ2 (n = 21, 2.9 %), and PCDH19 (n = 17, 2.4 %). The rate of ultra-rare variants (< 0.5 %) was higher in the NGS era (52 %) than that in the initial phase (36 %). The potential therapeutic yields with precision therapy and antiseizure drug modification were defined in 34.5 % and 56.2 % in genetic-EO-DEEs, respectively. The diagnostic model provided an etiology-specific diagnosis at a rate of 78.7 %: structural (nongenetic) (31.4 %), genetic (38.5 %), metabolic (6.1 %), and immune-infectious (2.8 %). Based on a cost-effectiveness analysis, the presented diagnostic model indicated the early implementation of whole-exome sequencing for EO-DEEs. Significance: In the present cohort, the higher rate (48.3 %) of gene-related EO-DEE diagnoses in the NGS era provides a potential therapeutic management plan for more patients. © 2024 British Epilepsy Association