100 results on '"Tuysuz B"'
Search Results
2. Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity
- Author
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Bachmann-Gagescu, R, Dempsey, J C, Phelps, I G, OʼRoak, B J, Knutzen, D M, Rue, T C, Ishak, G E, Isabella, C R, Gorden, N, Adkins, J, Boyle, E A, de Lacy, N, OʼDay, D, Alswaid, A, Ramadevi A, Radha, Lingappa, L, Lourenço, C, Martorell, L, Garcia-Cazorla, À, Ozyürek, H, Haliloğlu, G, Tuysuz, B, Topçu, M, Chance, P, Parisi, M A, Glass, I A, Shendure, J, and Doherty, D
- Published
- 2015
- Full Text
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3. Clinical and genetic features of 13 patients with mucopolysaccarhidosis type IIIB: Description of two novel NAGLU gene mutations
- Author
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Ozkinay, F., primary, Emecen, D.A., additional, Kose, M., additional, Isik, E., additional, Bozaci, A.E., additional, Canda, E., additional, Tuysuz, B., additional, Zubarioglu, T., additional, Atik, T., additional, and Onay, H., additional
- Published
- 2021
- Full Text
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4. Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy
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Chatron, N, Becker, F, Morsy, H, Schmidts, M, Hardies, K, Tuysuz, B, Roselli, S, Najafi, M, Alkaya, DU, Ashrafzadeh, F, Nabil, A, Omar, T, Maroofian, R, Karimiani, EG, Hussien, H, Kok, F, Ramos, L, Gunes, N, Bilguvar, K, Labalme, A, Alix, E, Sanlaville, D, de Bellescize, J, Poulat, A-L, EuroEpinomics-RES consortium AR working group, Moslemi, A-R, Lerche, H, May, P, Lesca, G, Weckhuysen, S, Tajsharghi, H, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], and University of Luxembourg: High Performance Computing - ULHPC [research center]
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cleft palate ,Epilepsy ,Hypsarrhythmia ,omphalocele ,GAD1 ,Suppression-burs ,Developmental Syndrome ,Genetics & genetic processes [F10] [Life sciences] ,Génétique & processus génétiques [F10] [Sciences du vivant] ,arthrogryposis - Abstract
Developmental and Epileptic Encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathies caused by bi-allelic loss of function variants in GAD1, as presented by eleven patients from 6 independent consanguineous families. Seizure onset occurred in the two first months of life in all patients. All 10 patients from whom early disease history was available, presented seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early electroencephalography showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1-/- mouse model. Four patients died before four years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the γ-aminobutyric acid (GABA) metabolism as it catalyzes the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele.
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- 2020
5. A rare cause of recurrent and serious venous thromboembolism: Klinefelterʼs syndrome: PO 399
- Author
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Ozdemir, N, Tuysuz, B, Evliyaoglu, O, Avar, O, Tuysuz, G, and Celkan, T
- Published
- 2013
6. Omani-type spondyloepiphyseal dysplasia with cardiac involvement caused by a missense mutation in CHST3
- Author
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Tuysuz, B, Mizumoto, S, Sugahara, K, Çelebi, A, Mundlos, S, and Turkmen, S
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- 2009
- Full Text
- View/download PDF
7. Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and Costello syndrome
- Author
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Schulz, A L, Albrecht, B, Arici, C, van der Burgt, I, Buske, A, Gillessen-Kaesbach, G, Heller, R, Horn, D, Hübner, C A, Korenke, G C, König, R, Kress, W, Krüger, G, Meinecke, P, Mücke, J, Plecko, B, Rossier, E, Schinzel, A, Schulze, A, Seemanova, E, Seidel, H, Spranger, S, Tuysuz, B, Uhrig, S, Wieczorek, D, Kutsche, K, and Zenker, M
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- 2008
8. Distinct phenotypes within TRPV4-associated disorders in the infantile period
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Tuysuz, B., Gunes, N., Yesil, G., Emre OZER, Uludag-Alkaya, D., Pehlivan, D., and Lupski, J.
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TÜYSÜZ B., Gunes N., Yesil G., Ozer E., Uludag-Alkaya D., Pehlivan D., Lupski J., -Distinct phenotypes within TRPV4-associated disorders in the infantile period-, 51st Conference of the European-Society-of-Human-Genetics (ESHG) in conjunction with the European Meeting on Psychosocial Aspects of Genetics (EMPAG), Milan, İtalya, 16 - 19 Haziran 2018, cilt.27, ss.132 - Published
- 2019
9. Severe speech delay in Cohen Syndrome: three novel mutations and the long-term follow-up of nine patients
- Author
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Akdeniz, B., Nilay Gunes, Uludag, D., Ercan-Sencicek, G., Caglayan, O., Bilguvar, K., and Tuysuz, B.
- Published
- 2019
10. Ankle2, A Target of Zika Virus, Controls Asymmetric Cell Division of Neuroblasts and Uncovers a Novel Microcephaly Pathway
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Link, N., primary, Chung, H., additional, Jolly, A., additional, Withers, M., additional, Tepe, B., additional, Arenkiel, B.R., additional, Shah, P.S., additional, Krogan, N.J., additional, Aydin, H., additional, Geckinli, B.B., additional, Tos, T., additional, Isikay, S., additional, Tuysuz, B., additional, Mochida, G.H., additional, Thomas, A.X., additional, Clark, R.D., additional, Mirzaa, G.M., additional, Lupski, J.R., additional, and Bellen, H.J., additional
- Published
- 2019
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11. Chondrodysplasia with multiple dislocations: comprehensive study of a series of 30 cases
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Ranza, E., Huber, C., Levin, N., Baujat, G., Bole-Feysot, C., Nitschke, P., Masson, C., Alanay, Y., Al-Gazali, L., Bitoun, P., Boute, O., Campeau, P., Coubes, C., McEntagart, M., Elcioglu, N., Faivre, Laurence, Gezdirici, A., Johnson, D., Mihci, E., Nur, B., Perrin, L., Quelin, C., Terhal, P., Tuysuz, B., Cormier-Daire, V., Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Hôpital Universitaire de Genève, Plateforme de génomique [Necker], Structure Fédérative de Recherche Necker ( SFR Necker - UMS 3633 / US24 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Plate Forme Paris Descartes de Bioinformatique ( BIP-D ), Université Paris Descartes - Paris 5 ( UPD5 ), Department of Pediatrics, Istanbul Faculty of Medicine, Department of Pediatrics, Faculty of Medicine and Health Sciences, UAE University, Service de Pédiatrie [Jean Verdier], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris 13 ( UP13 ) -Hôpital Jean Verdier, Service de Génétique clinique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Département de Pédiatrie [CHU Sainte -Justine Montréal], Université de Montréal-CHU Sainte Justine [Montréal], Service de Génétique Clinique, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Head of the Department of Medical Genetics, Department of Pediatric Genetics, Marmara University Medical Faculty, Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Service de génétique clinique [Debré], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, CHU Pontchaillou [Rennes], Wilhelmina Childrens Hosp, Pediatrics, Istanbul University Cerrahpasa, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme de génomique [SFR Necker], Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Plate Forme Paris Descartes de Bioinformatique (BIP-D), Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Sainte Justine [Montréal], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Sheffield Children's NHS Foundation Trust, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Assistance publique - Hôpitaux de Paris (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré
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Adult ,Male ,Spondyloepimetaphyseal Dysplasia ,Adolescent ,Joint Dislocations ,Osteochondrodysplasias ,Gene ,Catel-Manzke Syndrome ,Intellectual Disability ,Exome Sequencing ,Proteoglycan Synthesis ,Humans ,Child ,[ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics ,Genetic Association Studies ,Larsen-Syndrome ,Targeted Ngs ,Joint Laxity ,Infant, Newborn ,Infant ,Phenotypic Spectrum ,Musculoskeletal Abnormalities ,Radiography ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Child, Preschool ,Chondrodysplasia ,Genotype-Phenotype Correlation ,Deficiency ,Female ,Proteoglycans ,Desbuquois Dysplasia ,Mutations - Abstract
IF 3.326; International audience; The group of chondrodysplasia with multiple dislocations includes several entities, characterized by short stature, dislocation of large joints, hand and/or vertebral anomalies. Other features, such as epiphyseal or metaphyseal changes, cleft palate, intellectual disability are also often part of the phenotype. In addition, several conditions with overlapping features are related to this group and broaden the spectrum. The majority of these disorders have been linked to pathogenic variants in genes encoding proteins implicated in the synthesis or sulfation of proteoglycans (PG). In a series of 30 patients with multiple dislocations, we have performed exome sequencing and subsequent targeted analysis of 15 genes, implicated in chondrodysplasia with multiple dislocations, and related conditions. We have identified causative pathogenic variants in 60% of patients (18/30); when a clinical diagnosis was suspected, this was molecularly confirmed in 53% of cases. Forty percent of patients remain without molecular etiology. Pathogenic variants in genes implicated in PG synthesis are of major importance in chondrodysplasia with multiple dislocations and related conditions. The combination of hand features, growth failure severity, radiological aspects of long bones and of vertebrae allowed discrimination among the different conditions. We propose key diagnostic clues to the clinician.
- Published
- 2017
12. A New Target Radar Cross Section Based Passive Radar Surveillance Receiver Positioning Algorithm on Real Terrain Maps
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Tuysuz, B., primary
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- 2018
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13. First Genetic Screening for Maternal Uniparental Disomy of Chromosome 7 in Turkish Silver-Russell Syndrome Patients
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Karaca, E., Tuysuz, B., Pehlivan, S., Ozkinay, F., and Ege Üniversitesi
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Silver-Russell Syndrome ,congenital, hereditary, and neonatal diseases and abnormalities ,parasitic diseases ,Maternal UPD7 ,Original Article ,Microsatellite Markers ,Silver–Russell Syndrome ,Intrauterine Growth Retardation - Abstract
WOS: 000320852500003, PubMed ID: 23429302, Objective: Silver-Russell syndrome (SRS) is a clinically and genetically heterogeneous syndrome which is characterized by severe intrauterine and postnatal growth retardation, and typical characteristic facial dysmorphisms. It has been associated with maternal uniparental disomy (UPD) for chromosome 7 and hypomethylation of imprinting control region 1 (IGF2/H19) in 11p15. UPD refers to the situation in which both copies of a chromosome pair have originated from one parent. UPD can be presented both as partial heterodisomy and isodisomy. The aim of this study was to determine the maternal UPD7 (matUPD7) in 13 Turkish SRS patients. Methods: Genotyping for matUPD7 was performed with microsatellite markers by polymerase chain reaction. Findings: The maternal UPD7 including the entire chromosome was identified in 1/13 (7.6 %) of individuals within SRS patients. There were no significant differences between clinical features of matUPD7 case and other SRS cases except congenital heart defects. Conclusion: It is often difficult to establish diagnosis of a child with intrauterine growth retardation (IUGR), growth failure and dysmorphic features. Thus, screening for matUPD7 in IUGR children with growth failure and mild SRS features might be a valuable diagnostic tool.
- Published
- 2012
14. Autosomal recessive Robinow syndrome is caused by homozygous mutations in ROR2
- Author
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Afzal, A.R., Rajab, A., Fenske, C.D., Oldridge, M., Elanko, N., Ternes-Pereira, E., Tuysuz, B., Murday, V.A., Patton, M.A., Wilkie, A.O.M., and Jeffery, S.
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Genetic research -- Analysis ,Human genetics -- Research ,Genetic disorders -- Research ,Dysplasia -- Genetic aspects ,Biological sciences - Published
- 2000
15. Molecular analysis of 82 mucopolysaccharidosis type I patients: multinational spectrum in the european population and identification of 28 novel mutations
- Author
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Bertola F, Parini R, Casati G, Tylki Szymanska, Okur I, Tuysuz B, Dalmau J, Gonzales Meneses A, Antuzzi D, Barone R, Dionisi Vici C, Donati A, Filocamo M, Gabrielli O, Scarpa M, Uziel G, Biondi A., PARENTI, GIANCARLO, Bertola, F, Parini, R, Casati, G, Tylki, Szymanska, Okur, I, Tuysuz, B, Dalmau, J, Gonzales Meneses, A, Antuzzi, D, Barone, R, Dionisi Vici, C, Donati, A, Filocamo, M, Gabrielli, O, Parenti, Giancarlo, Scarpa, M, Uziel, G, and Biondi, A.
- Published
- 2008
16. Mutations in the Gene Encoding IFT Dynein Complex Component WDR34 Cause Jeune Asphyxiating Thoracic Dystrophy
- Author
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Schmidts, M., Vodopiutz, J., Christou-Savina, S., Cortes, C., McInerney-Leo, A., Emes, R.D., Arts, H.H., Tuysuz, B., D'Silva, J., Leo, P.J., Giles, T.C., Oud, M.M., Harris, J.A., Koopmans, M., Marshall, M., Elcioglu, N., Kuechler, A., Bockenhauer, D., Moore, A.T., Wilson, L., Janecke, A.R., Hurles, M.E., Emmet, W., Gardiner, B., Streubel, B., Dopita, B., Zankl, A., Kayserili, H., Scambler, P.J., Brown, M.A., Beales, P.L., Wicking, C., Uk10K, ., Duncan, E.L., and Mitchison, H.M.
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Proteomics ,Cytoplasmic Dyneins ,Axoneme ,Ellis-Van Creveld Syndrome ,Protein Conformation ,1.1 Normal biological development and functioning ,Medical and Health Sciences ,White People ,Rare Diseases ,Asian People ,Underpinning research ,Animals ,Humans ,Exome ,Cilia ,Child ,Cytoskeleton ,Pediatric ,Genetics & Heredity ,Whites ,Chlamydomonas ,Intracellular Signaling Peptides and Proteins ,Infant ,Exons ,Biological Sciences ,Newborn ,Asians ,UK10K ,Mutation ,Genetics and epigenetic pathways of disease Renal disorder [NCMLS 6] ,Generic health relevance ,Carrier Proteins - Abstract
Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 invitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery.
- Published
- 2013
17. Molecular analysis of 82 mucopolysaccharidosis type I patients: Mutational spectrum in the European population and identification of 28 novel mutations
- Author
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Bertola, F., Parini, R., Casati, G., Tylki-Szymanska, A., Okur, I., Tuysuz, B., Dalmau, J., Gonzales, Meneses A., Antuzzi, D., Rita Barone, Dionisi, Vici C., Donati, A., Filocamo, M., Gabrielli, O., Parenti, G., Scarpa, M., Uziel, G., and Biondi, A.
- Published
- 2008
18. Detection of Y chromosomal material in patients with a 45,X karyotype by
- Author
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Semerci, CN, Satiroglu-Tufan, NL, Turan, S, Bereket, A, Tuysuz, B, Yilmaz, E, Kayserili, H, Karaman, B, Semiz, S, Duzcan, F, and Bagci, H
- Subjects
45,X karyotype ,Y sequences ,PCR ,gonadoblastoma ,virilisation - Abstract
A 45,X karyotype is one of the common chromosomal abnormalities characterized by short stature, lack of development of secondary sexual characteristics, webbed neck and cubitus valgus. This phenotype was described by Turner in 1938 and was called Turner syndrome (TS). About 40-60% of the patients with TS phenotype have a 45,X karyotype, the rest either have a structurally abnormal X or Y chromosome or mosaicism with a second cell line. Determination of Y chromosome derivatives in patients with a 45,X karyotype is important for the management of these patients due to increased risk of gonadoblastoma. Low level mosaicisim of Y chromosome may be missed by cytogenetic methods. The aim of our study is to analyze cryptic Y chromosome derivatives using Y specific sequences in 40 Turkish patients with a pure 45,X karyotype. Fourteen different Y specific sequences along the Y chromosome were selected for the detection of cryptic Y chromosome material by PCR analysis. The present study demonstrated that 2 patients with a 45,X karyotype (5%) have Y specific sequences except sex releated region Y (SRY). One of them had displayed enhanced virilisation whereas other showed no virilisation. In conclusion, it has been found by PCR analysis that 5% of patients with a 45,X karyotype have Y chromosome sequences in the absence of any marker chromosome by cytogenetic analysis. The data also suggest that the patients with a 45,X karyotype should be analyzed for the presence of Y chromosome derivatives by sensitive methods, such as PCR, in order to calculate the future risk of developing gonadoblastoma.
- Published
- 2007
19. Development of a passive VHF radar system using software-defined radio for equatorial plasma instability studies
- Author
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Tuysuz, B., primary, Urbina, J., additional, and Lind, F. D., additional
- Published
- 2013
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20. First results from the coherent-scatter atmospheric passive radar imager (CAPRI) for passive radio sensing of equatorial plasma instabilities near the Peruvian andes
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Tuysuz, B., primary, Urbina, J., additional, and Lind, F. D., additional
- Published
- 2013
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21. Loss-of-function mutations in ATP6V0A2 impair vesicular trafficking, tropoelastin secretion and cell survival
- Author
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Hucthagowder, V., primary, Morava, E., additional, Kornak, U., additional, Lefeber, D. J., additional, Fischer, B., additional, Dimopoulou, A., additional, Aldinger, A., additional, Choi, J., additional, Davis, E. C., additional, Abuelo, D. N., additional, Adamowicz, M., additional, Al-Aama, J., additional, Basel-Vanagaite, L., additional, Fernandez, B., additional, Greally, M. T., additional, Gillessen-Kaesbach, G., additional, Kayserili, H., additional, Lemyre, E., additional, Tekin, M., additional, Turkmen, S., additional, Tuysuz, B., additional, Yuksel-Konuk, B., additional, Mundlos, S., additional, Van Maldergem, L., additional, Wevers, R. A., additional, and Urban, Z., additional
- Published
- 2009
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22. Mutation and phenotypic spectrum in patients with cardio‐facio‐cutaneous and Costello syndrome
- Author
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Schulz, AL, primary, Albrecht, B, additional, Arici, C, additional, Van Der Burgt, I, additional, Buske, A, additional, Gillessen‐Kaesbach, G, additional, Heller, R, additional, Horn, D, additional, Hübner, CA, additional, Korenke, GC, additional, König, R, additional, Kress, W, additional, Krüger, G, additional, Meinecke, P, additional, Mücke, J, additional, Plecko, B, additional, Rossier, E, additional, Schinzel, A, additional, Schulze, A, additional, Seemanova, E, additional, Seidel, H, additional, Spranger, S, additional, Tuysuz, B, additional, Uhrig, S, additional, Wieczorek, D, additional, Kutsche, K, additional, and Zenker, M, additional
- Published
- 2007
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23. Progressive systemic scleroderma in an infant with partial phenylketonuria
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Haktan, M., Aydin, A., Bahat, H., Tuysuz, B., Yazici, H., and Altay, S.
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- 1989
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24. PROGNOSTIC FACTORS IN MENINGOCOCCAL DISEASE AND A NEW SCORING SYSTEM
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Tuysuz, B., primary
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- 1994
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25. Two cases of partial trisomy 10q syndrome due to a familial 10;20 translocation
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Tuysuz, B., Hacihanefioglu, S., Asli Silahtaroglu, Yilmaz, S., Deviren, A., and Cenani, A.
26. Phenotypic and Molecular Characterization of Cockayne Syndrome; A Spotlight to Mild Cases
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Yesil, G., Enes Akyuz, Gunes, N., Lessel, D., Kubisch, C., Tuysuz, B., and YEŞİL, Gözde
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YEŞİL G., GÜNEŞ N., Akyüz E., Lesser D., Kublach C., TÜYSÜZ B., -Phenotypic and Molecular Characterization of Cockayne Syndrome A Spotlight to Mild Cases-, ESHG, 27 - 30 May 2017
27. Abnormalities in the cerebral arterial system in osteogenesis imperfecta
- Author
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Albayram, S., Kizilkic, O., Yilmaz, H., Tuysuz, B., Naci Kocer, and Islak, C.
28. Variant characterisation and clinical profile in a large cohort of patients with Ellis-van Creveld syndrome and a family with Weyers acrofacial dysostosis.
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Altunoglu U, Palencia-Campos A, Güneş N, Turgut GT, Nevado J, Lapunzina P, Valencia M, Iturrate A, Otaify G, Elhossini R, Ashour A, K Amin A, Elnahas RF, Fernandez-Nuñez E, Flores CL, Arias P, Tenorio J, Chamorro Fernández CI, Güven Y, Özsu E, Eklioğlu BS, Ibarra-Ramirez M, Diness BR, Burnyte B, Ajmi H, Yüksel Z, Yıldırım R, Ünal E, Abdalla E, Aglan M, Kayserili H, Tuysuz B, and Ruiz-Pérez V
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- Humans, Male, Female, Child, Membrane Proteins genetics, Mutation, Child, Preschool, Zinc Finger Protein Gli3 genetics, Adolescent, Adult, Nerve Tissue Proteins genetics, Cohort Studies, Infant, Proteins genetics, Retrospective Studies, Intercellular Signaling Peptides and Proteins, Ellis-Van Creveld Syndrome genetics, Ellis-Van Creveld Syndrome pathology, Phenotype, Pedigree
- Abstract
Background: Ellis-van Creveld syndrome (EvC) is a recessive disorder characterised by acromesomelic limb shortening, postaxial polydactyly, nail-teeth dysplasia and congenital cardiac defects, primarily caused by pathogenic variants in EVC or EVC2 . Weyers acrofacial dysostosis (WAD) is an ultra-rare dominant condition allelic to EvC. The present work aimed to enhance current knowledge on the clinical manifestations of EvC and WAD and broaden their mutational spectrum., Methods: We conducted molecular studies in 46 individuals from 43 unrelated families with a preliminary clinical diagnosis of EvC and 3 affected individuals from a family with WAD and retrospectively analysed clinical data. The deleterious effect of selected variants of uncertain significance was evaluated by cellular assays., Main Results: We identified pathogenic variants in EVC/EVC2 in affected individuals from 41 of the 43 families with EvC. Patients from each of the two remaining families were found with a homozygous splicing variant in WDR35 and a de novo heterozygous frameshift variant in GLI3 , respectively. The phenotype of these patients showed a remarkable overlap with EvC. A novel EVC2 C-terminal truncating variant was identified in the family with WAD. Deep phenotyping of the cohort recapitulated 'classical EvC findings' in the literature and highlighted findings previously undescribed or rarely described as part of EvC., Conclusions: This study presents the largest cohort of living patients with EvC to date, contributing to better understanding of the full clinical spectrum of EvC. We also provide comprehensive information on the EVC / EVC2 mutational landscape and add GLI3 to the list of genes associated with EvC-like phenotypes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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29. Metabolic and other morbid complications in congenital generalized lipodystrophy type 4.
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Akinci G, Alyaarubi S, Patni N, Alhashmi N, Al-Shidhani A, Prodam F, Gagne N, Babalola F, Al Senani A, Muniraj K, Elsayed SM, Beghini M, Saydam BO, Allawati M, Vaishnav MS, Can E, Simsir IY, Sorkina E, Dursun F, Kamrath C, Cavdar U, Chakraborty PP, Dogan OA, Al Hosin A, Al Maimani A, Comunoglu N, Hamed A, Huseinbegovic T, Scherer T, Curtis J, Brown RJ, Topaloglu H, Simha V, Wabitsch M, Tuysuz B, Oral EA, Akinci B, and Garg A
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- Humans, Male, Female, Adolescent, Child, Infant, Child, Preschool, Adult, Young Adult, Arrhythmias, Cardiac genetics, Arrhythmias, Cardiac pathology, Hypertriglyceridemia genetics, Hypertriglyceridemia complications, Hypertriglyceridemia pathology, Lipodystrophy, Congenital Generalized genetics, Lipodystrophy, Congenital Generalized complications, Lipodystrophy, Congenital Generalized pathology, RNA-Binding Proteins
- Abstract
Morbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra-rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346-3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias., (© 2024 Wiley Periodicals LLC.)
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- 2024
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30. Association of Antenatal Evaluations with Postmortem and Genetic Findings in the Series of Fetal Osteogenesis Imperfecta.
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Senturk L, Gulec C, Sarac Sivrikoz T, Kayserili H, Kalelioglu IH, Avci S, Has R, Coucke P, Kalayci T, Wollnik B, Karaman B, Toksoy G, Symoens S, Yigit G, Yuksel A, Basaran S, Tuysuz B, Altunoglu U, and Uyguner ZO
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- Humans, Female, Pregnancy, Ultrasonography, Prenatal, Collagen Type I, alpha 1 Chain, Tacrolimus Binding Proteins genetics, Male, Collagen Type I genetics, Autopsy, Prolyl Hydroxylases genetics, Adult, Membrane Glycoproteins, Membrane Proteins, Proteoglycans, Osteogenesis Imperfecta genetics, Osteogenesis Imperfecta diagnostic imaging
- Abstract
Introduction: Counseling osteogenesis imperfecta (OI) pregnancies is challenging due to the wide range of onsets and clinical severities, from perinatal lethality to milder forms detected later in life., Methods: Thirty-eight individuals from 36 families were diagnosed with OI through prenatal ultrasonography and/or postmortem clinical and radiographic findings. Genetic analysis was conducted on 26 genes associated with OI in these subjects that emerged over the past 20 years; while some genes were examined progressively, all 26 genes were examined in the group where no pathogenic variations were detected., Results: Prenatal and postnatal observations both consistently showed short limbs in 97%, followed by bowing of the long bones in 89%. Among 32 evaluated cases, all exhibited cranial hypomineralization. Fractures were found in 29 (76%) cases, with multiple bones involved in 18 of them. Genetic associations were disclosed in 27 families with 22 (81%) autosomal dominant and five (19%) autosomal recessive forms, revealing 25 variants in six genes (COL1A1, COL1A2, CREB3L1, P3H1, FKBP10, and IFITM5), including nine novels. Postmortem radiological examination showed variability in intrafamily expression of CREBL3- and P3H1-related OI., Conclusion: Prenatal diagnosis for distinguishing OI and its subtypes relies on factors such as family history, timing, ultrasound, genetics, and postmortem evaluation., (© 2024 S. Karger AG, Basel.)
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- 2024
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31. functional outcome in late adolescence/early adulthood of patients with autism spectrum disorder and its relationships with parental burnout and depression: A preliminary multi-center, cross-sectional study.
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Kutuk MO, Tufan AE, Kilicaslan F, Vural P, Gokcen C, Alsen Guney S, Kutuk B, Ozyurt G, Inal N, Mutluer T, Acikalin EY, Ozer FH, Pamuk EN, Yesilmese SC, Karadag M, Hangul Z, Bilginer C, Sahin N, Bilac O, Kandemir H, Ercan ES, Eseroglu Soylemez T, Acikel SB, Guler Aksu G, Dag P, Toros F, Mutlu C, Kardas O, Kardas B, Kizildag S, Demirci E, Ozmen S, Sevicin L, Karagoz YS, Isik U, Aktepe E, Altun H, Yektas Ç, Polat Tuysuz B, Buber A, Cansiz MA, Ogutlu H, Eray S, Taner HA, Altintas E, and Kutuk O
- Abstract
The aim of this study is to determine the functioning of adults with autism spectrum disorders (ASDs) diagnosed in childhood and depression and burnout levels among their parents. A total of 261 adults with ASDs and their parents were recruited for the study. Both parents completed the Beck Depression and Maslach Burnout Inventories and reported the functioning of their adult offspring with ASDs. Only 5.4 % of our sample reported "good" or "very good" outcomes. The most common psychiatric comorbidities were intellectual disabilities and attention-deficit/hyperactivity disorder. Maternal burnout and depression scores were significantly elevated compared to those of fathers. There is an undeniable urgent need for more research to identify the needs of adults and families suffering from ASD. Modifications for those with ASD may have to be made for support in workplaces, achieving driving licenses, using public transportation and attendance at tertiary education., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)
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- 2023
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32. Biallelic frameshift variants in PHLDB1 cause mild-type osteogenesis imperfecta with regressive spondylometaphyseal changes.
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Tuysuz B, Uludag Alkaya D, Geyik F, Alaylıoğlu M, Kasap B, Kurugoğlu S, Akman YE, Vural M, and Bilguvar K
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- Humans, Child, Preschool, Heterozygote, Phenotype, Frameshift Mutation genetics, Collagen Type I genetics, Mutation, Nerve Tissue Proteins genetics, Intracellular Signaling Peptides and Proteins genetics, Osteogenesis Imperfecta genetics, Fractures, Bone
- Abstract
Background: Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders characterised by susceptibility to fractures, primarily due to defects in type 1 collagen. The aim of this study is to present a novel OI phenotype and its causative candidate gene., Methods: Whole-exome sequencing and clinical evaluation were performed in five patients from two unrelated families. PHLDB1 mRNA expression in blood and fibroblasts was investigated by real-time PCR, and western blot analysis was further performed on skin fibroblasts., Results: The common findings among the five affected children were recurrent fractures and/or osteopaenia, platyspondyly, short and bowed long bones, and widened metaphyses. Metaphyseal and vertebral changes regressed after early childhood, and no fractures occurred under bisphosphonate treatment. We identified biallelic NM_001144758.3:c.2392dup and NM_001144758.3:c.2690_2693del pathogenic variants in PHLDB1 in the affected patients, respectively, in the families; parents were heterozygous for these variants. PHLDB1 encodes pleckstrin homology-like domain family B member-1 (PHLDB1) protein, which has a role in insulin-dependent Akt phosphorylation. Compared with controls, a decrease in the expression levels of PHLDB1 in the blood and skin fibroblast samples was detected. Western blot analysis of cultured fibroblasts further confirmed the loss of PHLDB1., Conclusion: Two biallelic frameshift variants in the candidate gene PHLDB1 were identified in independent families with a novel, mild-type, autosomal recessive OI. The demonstration of decreased PHLDB1 mRNA expression levels in blood and fibroblast samples supports the hypothesis that PHLDB1 pathogenic variants are causative for the observed phenotype., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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33. The clinical phenotype of Koolen-de Vries syndrome in Turkish patients and literature review.
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Karamik G, Tuysuz B, Isik E, Yilmaz A, Alanay Y, Sunamak EC, Durmusalioglu EA, Ozkinay F, Cetin GO, Ozturk N, Mihci E, and Nur B
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- Humans, Chromosome Deletion, Rare Diseases genetics, Phenotype, Chromosomes, Human, Pair 17 genetics, Abnormalities, Multiple diagnosis, Abnormalities, Multiple epidemiology, Abnormalities, Multiple genetics, Intellectual Disability diagnosis, Intellectual Disability epidemiology, Intellectual Disability genetics
- Abstract
Koolen-de Vries syndrome (KdVS) is a rare multisystemic disorder caused by a microdeletion on chromosome 17q21.31 including KANSL1 gene or intragenic pathogenic variants in KANSL1 gene. Here, we describe the clinical and genetic spectrum of eight Turkish children with KdVS due to a de novo 17q21.31 deletion, and report on several rare/new conditions. Eight patients from unrelated families aged between 17 months and 19 years enrolled in this study. All patients evaluated by a clinical geneticist, and the clinical diagnosis were confirmed by molecular karyotyping. KdVS patients had some common distinctive facial features. All patients had neuromotor retardation, and speech and language delay. Epilepsy, structural brain anomalies, ocular, ectodermal, and musculoskeletal findings, and friendly personality were remarkable in more than half of the patients. Hypertension, hypothyroidism, celiac disease, and postaxial polydactyly were among the rare/new conditions. Our study contributes to the clinical spectrum of patients with KdVS, while also provide a review by comparing them with previous cohort studies., (© 2023 Wiley Periodicals LLC.)
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- 2023
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34. Clinical features of generalized lipodystrophy in Turkey: A cohort analysis.
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Yildirim Simsir I, Tuysuz B, Ozbek MN, Tanrikulu S, Celik Guler M, Karhan AN, Denkboy Ongen Y, Gunes N, Soyaltin UE, Altay C, Nur B, Ozalkak S, Akgun Dogan O, Dursun F, Pekkolay Z, Eren MA, Usta Y, Ozisik S, Ozgen Saydam B, Adiyaman SC, Unal MC, Gungor Semiz G, Turan I, Eren E, Kayserili H, Jeru I, Vigouroux C, Atik T, Onay H, Ozen S, Arioglu Oral E, and Akinci B
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- Female, Humans, Turkey epidemiology, Cohort Studies, Kaplan-Meier Estimate, Lipodystrophy, Congenital Generalized, Diabetes Mellitus, Myocardial Infarction complications, Renal Insufficiency, Chronic complications, Hypertriglyceridemia complications, Lipodystrophy
- Abstract
Aim: To describe the Turkish generalized lipodystrophy (GL) cohort with the frequency of each complication and the death rate during the period of the follow-up., Methods: This study reports on 72 patients with GL (47 families) registered at different centres in Turkey that cover all regions of the country. The mean ± SD follow-up was 86 ± 78 months., Results: The Kaplan-Meier estimate of the median time to diagnosis of diabetes and/or prediabetes was 16 years. Hyperglycaemia was not controlled in 37 of 45 patients (82.2%) with diabetes. Hypertriglyceridaemia developed in 65 patients (90.3%). The Kaplan-Meier estimate of the median time to diagnosis of hypertriglyceridaemia was 14 years. Hypertriglyceridaemia was severe (≥ 500 mg/dl) in 38 patients (52.8%). Seven (9.7%) patients suffered from pancreatitis. The Kaplan-Meier estimate of the median time to diagnosis of hepatic steatosis was 15 years. Liver disease progressed to cirrhosis in nine patients (12.5%). Liver disease was more severe in congenital lipodystrophy type 2 (CGL2). Proteinuric chronic kidney disease (CKD) developed in 32 patients (44.4%) and cardiac disease in 23 patients (31.9%). Kaplan-Meier estimates of the median time to diagnosis of CKD and cardiac disease were 25 and 45 years, respectively. Females appeared to have a more severe metabolic disease, with an earlier onset of metabolic abnormalities. Ten patients died during the follow-up period. Causes of death were end-stage renal disease, sepsis (because of recurrent intestinal perforations, coronavirus disease, diabetic foot infection and following coronary artery bypass graft surgery), myocardial infarction, heart failure because of dilated cardiomyopathy, stroke, liver complications and angiosarcoma., Conclusions: Standard treatment approaches have only a limited impact and do not prevent the development of severe metabolic abnormalities and early onset of organ complications in GL., (© 2023 John Wiley & Sons Ltd.)
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- 2023
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35. Biallelic BICD2 variant is a novel candidate for Cohen-like syndrome.
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Caglayan AO, Tuysuz B, Gül E, Alkaya DU, Yalcinkaya C, Gleeson JG, Bilguvar K, and Gunel M
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- Genes, Dominant, Humans, Microtubule-Associated Proteins genetics, Mutation, Mutation, Missense, Intellectual Disability genetics, Muscular Atrophy, Spinal genetics
- Abstract
Heterozygous mutations in Bicaudal D2 Drosophila homolog 2 (BICD2) gene, encodes a vesicle transport protein involved in dynein-mediated movement along microtubules, are responsible for an exceedingly rare autosomal dominant spinal muscular atrophy type 2A which starts in the childhood and predominantly effects lower extremities. Recently, a more severe form, type 2B, has also been described. Here, we present a patient born to a consanguineous union and who suffered from intellectual disability, speech delay, epilepsy, happy facial expression, truncal obesity with tappering fingers, and joint hypermobility. Whole-exome sequencing analysis revealed a rare, homozygous missense mutation (c.731T>C; p.Leu244Pro) in BICD2 gene. This finding presents the first report in the literature for homozygous BICD2 mutations and its association with a Cohen-Like syndrome. Patients presenting with Cohen-Like phenotypes should be further interrogated for mutations in BICD2., (© 2022. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)
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- 2022
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36. A splice site mutation in the TSEN2 causes a new syndrome with craniofacial and central nervous system malformations, and atypical hemolytic uremic syndrome.
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Canpolat N, Liu D, Atayar E, Saygili S, Kara NS, Westfall TA, Ding Q, Brown BJ, Braun TA, Slusarski D, Karli Oguz K, Ozluk Y, Tuysuz B, Tastemel Ozturk T, Sever L, Sezerman OU, Topaloglu R, Caliskan S, Attanasio M, and Ozaltin F
- Subjects
- Animals, Endonucleases genetics, Female, Humans, Male, Mutation genetics, RNA, Transfer, Zebrafish genetics, Atypical Hemolytic Uremic Syndrome genetics, Microcephaly complications
- Abstract
Recessive mutations in the genes encoding the four subunits of the tRNA splicing endonuclease complex (TSEN54, TSEN34, TSEN15, and TSEN2) cause various forms of pontocerebellar hypoplasia, a disorder characterized by hypoplasia of the cerebellum and the pons, microcephaly, dysmorphisms, and other variable clinical features. Here, we report an intronic recessive founder variant in the gene TSEN2 that results in abnormal splicing of the mRNA of this gene, in six individuals from four consanguineous families affected with microcephaly, multiple craniofacial malformations, radiological abnormalities of the central nervous system, and cognitive retardation of variable severity. Remarkably, unlike patients with previously described mutations in the components of the TSEN complex, all the individuals that we report developed atypical hemolytic uremic syndrome (aHUS) with thrombotic microangiopathy, microangiopathic hemolytic anemia, thrombocytopenia, proteinuria, severe hypertension, and end-stage kidney disease (ESKD) early in life. Bulk RNA sequencing of peripheral blood cells of four affected individuals revealed abnormal tRNA transcripts, indicating an alteration of the tRNA biogenesis. Morpholino-mediated skipping of exon 10 of tsen2 in zebrafish produced phenotypes similar to human patients. Thus, we have identified a novel syndrome accompanied by aHUS suggesting the existence of a link between tRNA biology and vascular endothelium homeostasis, which we propose to name with the acronym TRACK syndrome (TSEN2 Related Atypical hemolytic uremic syndrome, Craniofacial malformations, Kidney failure)., (© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)
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- 2022
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37. Spondylometaepiphyseal Dysplasia Short Limb-Abnormal Calcification Type in Turkish Patients Reveals a Novel Mutation and New Features.
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Yilmaz Gulec E, Ali BR, John A, and Tuysuz B
- Abstract
Spondylometaepiphyseal dysplasia short limb-abnormal calcification type (SMED-SL/AC) is a rare autosomal recessive disorder. It is a severe dwarfism syndrome with a characteristic feature of progressive calcification of epiphyseal and other cartilaginous tissues. It is caused by pathogenic variants in the DDR2 gene encoding the discoidin domain receptor tyrosine kinase 2. Thus far, 37 cases and 8 pathogenic variants have been reported. Most of the reported cases are of Middle Eastern and Puerto Rican origins. Only one Turkish case has been reported previously with a novel truncating variant p.(R489*). Here, we report 2 new cases, 1 with a novel variant p.(S311G) and 1 with a splice site variant c.2283+1G>A. In addition, we reviewed a previously reported case, and sequencing of stored DNA revealed the recently reported nonsense variant p.(R489*) as the underlying cause. Therefore, our data increase the number of SMED-SL/AC Turkish patients with molecular results to 4. Furthermore, we compared the features of Turkish patients with other reported cases and expanded the characteristics of the disorder with new features such as triventricular hydrocephalus, intracranial hemorrhage, hypopigmentation of hair, dry and scaly skin, arthralgia, and hypocalcemia. We also compared the pathogenic variants of Turkish patients with other variants, aiming to explain the mechanism leading to a more severe and early fatal course in Turkish patients., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by S. Karger AG, Basel.)
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- 2022
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38. Two novel variants and follow-up findings in four children with Bloom syndrome from two families.
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Kasap B, Guclu-Geyik F, Uludag Alkaya D, Cetin G, and Tuysuz B
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- Child, Follow-Up Studies, Humans, Bloom Syndrome
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- 2022
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39. Effects of Long-Term Pamidronate Treatment on Bone Density and Fracture Rate in 65 Osteogenesis Imperfecta Patients.
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Yazan H, Güneş N, Akpınar E, Özyalvaç ON, Uludağ Akkaya D, and Tuysuz B
- Abstract
Objective: Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous disease characterized by recurrent fractures, blue sclera, and hearing loss. Bisphosphonate treatment has been reported to decrease the annual number of fractures and improve the quality of life in patients with OI. The aim of this study is to evaluate the effect of bisphosphonate treatment in the Turkish OI cohort., Methods: Sixty-five patients with OI, who were treated with pamidronate, were included in this study. The mean treatment duration was 47.1 ± 40 months (range:12-168 months). Bone mineral densitometry (BMD) and the mean number of annual fractures were compared before and after the treatment within groups, and the difference after treatment compared between the OI types., Results: After pamidronate treatment, a significant decrease in the mean annual fracture, along with an increase in BMD Z-score was detected in all patients. Treatment duration did not affect BMD Z-score. However, there was a significant decrease in the mean annual number of fractures after 5 years of treatment (P = .048). After treatment, the decrease in the number of fractures was significant in OI type 3, and the increase in BMD Z-score was significant in OI type 4 when compared with OI type 1. Besides, pamidronate treatment relieved pain, and also corrected the platyspondyly radiologically in all OI groups., Conclusion: We demonstrated that pamidronate treatment improves the quality of life by reducing the number of fractures, relieving pain, and also protecting from deformities in all patients with OI.
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- 2021
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40. Genome sequencing in families with congenital limb malformations.
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Elsner J, Mensah MA, Holtgrewe M, Hertzberg J, Bigoni S, Busche A, Coutelier M, de Silva DC, Elçioglu N, Filges I, Gerkes E, Girisha KM, Graul-Neumann L, Jamsheer A, Krawitz P, Kurth I, Markus S, Megarbane A, Reis A, Reuter MS, Svoboda D, Teller C, Tuysuz B, Türkmen S, Wilson M, Woitschach R, Vater I, Caliebe A, Hülsemann W, Horn D, Mundlos S, and Spielmann M
- Subjects
- Base Sequence, Cohort Studies, DNA Copy Number Variations, Gene Expression, Genetic Testing, Humans, Infant, Limb Deformities, Congenital metabolism, Limb Deformities, Congenital pathology, Male, Pedigree, Transcription Factors deficiency, Ubiquitin-Activating Enzymes deficiency, Whole Genome Sequencing, Genetic Heterogeneity, Homeodomain Proteins genetics, Limb Deformities, Congenital genetics, Mutation, Transcription Factors genetics, Ubiquitin-Activating Enzymes genetics
- Abstract
The extensive clinical and genetic heterogeneity of congenital limb malformation calls for comprehensive genome-wide analysis of genetic variation. Genome sequencing (GS) has the potential to identify all genetic variants. Here we aim to determine the diagnostic potential of GS as a comprehensive one-test-for-all strategy in a cohort of undiagnosed patients with congenital limb malformations. We collected 69 cases (64 trios, 1 duo, 5 singletons) with congenital limb malformations with no molecular diagnosis after standard clinical genetic testing and performed genome sequencing. We also developed a framework to identify potential noncoding pathogenic variants. We identified likely pathogenic/disease-associated variants in 12 cases (17.4%) including four in known disease genes, and one repeat expansion in HOXD13. In three unrelated cases with ectrodactyly, we identified likely pathogenic variants in UBA2, establishing it as a novel disease gene. In addition, we found two complex structural variants (3%). We also identified likely causative variants in three novel high confidence candidate genes. We were not able to identify any noncoding variants. GS is a powerful strategy to identify all types of genomic variants associated with congenital limb malformation, including repeat expansions and complex structural variants missed by standard diagnostic approaches. In this cohort, no causative noncoding SNVs could be identified.
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- 2021
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41. Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy.
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Chatron N, Becker F, Morsy H, Schmidts M, Hardies K, Tuysuz B, Roselli S, Najafi M, Alkaya DU, Ashrafzadeh F, Nabil A, Omar T, Maroofian R, Karimiani EG, Hussien H, Kok F, Ramos L, Gunes N, Bilguvar K, Labalme A, Alix E, Sanlaville D, de Bellescize J, Poulat AL, Moslemi AR, Lerche H, May P, Lesca G, Weckhuysen S, and Tajsharghi H
- Subjects
- Abnormalities, Multiple genetics, Female, Humans, Infant, Newborn, Male, Mutation, Pedigree, Epileptic Syndromes genetics, Epileptic Syndromes pathology, Epileptic Syndromes physiopathology, Glutamate Decarboxylase genetics
- Abstract
Developmental and epileptic encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathy caused by bi-allelic loss-of-function variants in GAD1, as presented by 11 patients from six independent consanguineous families. Seizure onset occurred in the first 2 months of life in all patients. All 10 patients, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1-/- mouse model. Four patients died before 4 years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the γ-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2020
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42. Mutations in ANKLE2, a ZIKA Virus Target, Disrupt an Asymmetric Cell Division Pathway in Drosophila Neuroblasts to Cause Microcephaly.
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Link N, Chung H, Jolly A, Withers M, Tepe B, Arenkiel BR, Shah PS, Krogan NJ, Aydin H, Geckinli BB, Tos T, Isikay S, Tuysuz B, Mochida GH, Thomas AX, Clark RD, Mirzaa GM, Lupski JR, and Bellen HJ
- Subjects
- Animals, Cell Division, Drosophila melanogaster metabolism, Humans, Mutation, Neural Stem Cells metabolism, Neural Stem Cells virology, Neurons cytology, Zika Virus, Asymmetric Cell Division physiology, Cell Polarity physiology, Membrane Proteins genetics, Microcephaly virology, Neurons metabolism, Nuclear Proteins genetics
- Abstract
The apical Par complex, which contains atypical protein kinase C (aPKC), Bazooka (Par-3), and Par-6, is required for establishing polarity during asymmetric division of neuroblasts in Drosophila, and its activity depends on L(2)gl. We show that loss of Ankle2, a protein associated with microcephaly in humans and known to interact with Zika protein NS4A, reduces brain volume in flies and impacts the function of the Par complex. Reducing Ankle2 levels disrupts endoplasmic reticulum (ER) and nuclear envelope morphology, releasing the kinase Ballchen-VRK1 into the cytosol. These defects are associated with reduced phosphorylation of aPKC, disruption of Par-complex localization, and spindle alignment defects. Importantly, removal of one copy of ballchen or l(2)gl suppresses Ankle2 mutant phenotypes and restores viability and brain size. Human mutational studies implicate the above-mentioned genes in microcephaly and motor neuron disease. We suggest that NS4A, ANKLE2, VRK1, and LLGL1 define a pathway impinging on asymmetric determinants of neural stem cell division., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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43. The Genomics of Arthrogryposis, a Complex Trait: Candidate Genes and Further Evidence for Oligogenic Inheritance.
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Pehlivan D, Bayram Y, Gunes N, Coban Akdemir Z, Shukla A, Bierhals T, Tabakci B, Sahin Y, Gezdirici A, Fatih JM, Gulec EY, Yesil G, Punetha J, Ocak Z, Grochowski CM, Karaca E, Albayrak HM, Radhakrishnan P, Erdem HB, Sahin I, Yildirim T, Bayhan IA, Bursali A, Elmas M, Yuksel Z, Ozdemir O, Silan F, Yildiz O, Yesilbas O, Isikay S, Balta B, Gu S, Jhangiani SN, Doddapaneni H, Hu J, Muzny DM, Boerwinkle E, Gibbs RA, Tsiakas K, Hempel M, Girisha KM, Gul D, Posey JE, Elcioglu NH, Tuysuz B, and Lupski JR
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Connectin genetics, Female, Gestational Age, Humans, Infant, Infant, Newborn, Male, Mosaicism, Pedigree, Ryanodine Receptor Calcium Release Channel genetics, Vesicular Transport Proteins genetics, Exome Sequencing, Young Adult, Arthrogryposis genetics, Arthrogryposis pathology, DNA Copy Number Variations, Genetic Markers, Genomics methods, Multifactorial Inheritance genetics, Mutation
- Abstract
Arthrogryposis is a clinical finding that is present either as a feature of a neuromuscular condition or as part of a systemic disease in over 400 Mendelian conditions. The underlying molecular etiology remains largely unknown because of genetic and phenotypic heterogeneity. We applied exome sequencing (ES) in a cohort of 89 families with the clinical sign of arthrogryposis. Additional molecular techniques including array comparative genomic hybridization (aCGH) and Droplet Digital PCR (ddPCR) were performed on individuals who were found to have pathogenic copy number variants (CNVs) and mosaicism, respectively. A molecular diagnosis was established in 65.2% (58/89) of families. Eleven out of 58 families (19.0%) showed evidence for potential involvement of pathogenic variation at more than one locus, probably driven by absence of heterozygosity (AOH) burden due to identity-by-descent (IBD). RYR3, MYOM2, ERGIC1, SPTBN4, and ABCA7 represent genes, identified in two or more families, for which mutations are probably causative for arthrogryposis. We also provide evidence for the involvement of CNVs in the etiology of arthrogryposis and for the idea that both mono-allelic and bi-allelic variants in the same gene cause either similar or distinct syndromes. We were able to identify the molecular etiology in nine out of 20 families who underwent reanalysis. In summary, our data from family-based ES further delineate the molecular etiology of arthrogryposis, yielded several candidate disease-associated genes, and provide evidence for mutational burden in a biological pathway or network. Our study also highlights the importance of reanalysis of individuals with unsolved diagnoses in conjunction with sequencing extended family members., (Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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44. Chondrodysplasia with multiple dislocations: comprehensive study of a series of 30 cases.
- Author
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Ranza E, Huber C, Levin N, Baujat G, Bole-Feysot C, Nitschke P, Masson C, Alanay Y, Al-Gazali L, Bitoun P, Boute O, Campeau P, Coubes C, McEntagart M, Elcioglu N, Faivre L, Gezdirici A, Johnson D, Mihci E, Nur BG, Perrin L, Quelin C, Terhal P, Tuysuz B, and Cormier-Daire V
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- Adolescent, Adult, Child, Child, Preschool, Female, Genetic Association Studies, Humans, Infant, Infant, Newborn, Intellectual Disability diagnosis, Intellectual Disability diagnostic imaging, Intellectual Disability physiopathology, Male, Musculoskeletal Abnormalities diagnosis, Musculoskeletal Abnormalities diagnostic imaging, Musculoskeletal Abnormalities physiopathology, Osteochondrodysplasias diagnosis, Osteochondrodysplasias diagnostic imaging, Osteochondrodysplasias physiopathology, Radiography, Exome Sequencing, Intellectual Disability genetics, Musculoskeletal Abnormalities genetics, Osteochondrodysplasias genetics
- Abstract
The group of chondrodysplasia with multiple dislocations includes several entities, characterized by short stature, dislocation of large joints, hand and/or vertebral anomalies. Other features, such as epiphyseal or metaphyseal changes, cleft palate, intellectual disability are also often part of the phenotype. In addition, several conditions with overlapping features are related to this group and broaden the spectrum. The majority of these disorders have been linked to pathogenic variants in genes encoding proteins implicated in the synthesis or sulfation of proteoglycans (PG). In a series of 30 patients with multiple dislocations, we have performed exome sequencing and subsequent targeted analysis of 15 genes, implicated in chondrodysplasia with multiple dislocations, and related conditions. We have identified causative pathogenic variants in 60% of patients (18/30); when a clinical diagnosis was suspected, this was molecularly confirmed in 53% of cases. Forty percent of patients remain without molecular etiology. Pathogenic variants in genes implicated in PG synthesis are of major importance in chondrodysplasia with multiple dislocations and related conditions. The combination of hand features, growth failure severity, radiological aspects of long bones and of vertebrae allowed discrimination among the different conditions. We propose key diagnostic clues to the clinician., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2017
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45. Disruptions in asymmetric centrosome inheritance and WDR62-Aurora kinase B interactions in primary microcephaly.
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Sgourdou P, Mishra-Gorur K, Saotome I, Henagariu O, Tuysuz B, Campos C, Ishigame K, Giannikou K, Quon JL, Sestan N, Caglayan AO, Gunel M, and Louvi A
- Subjects
- Animals, Brain abnormalities, Brain metabolism, Brain pathology, Cell Cycle genetics, Cell Cycle Proteins, Cell Differentiation genetics, Cell Proliferation, Consanguinity, Disease Models, Animal, Fluorescent Antibody Technique, Gene Expression, Humans, Male, Mice, Mice, Knockout, Microcephaly diagnostic imaging, Microcephaly pathology, Mutation, Neural Stem Cells metabolism, Pedigree, Whole Genome Sequencing, Aurora Kinase B genetics, Centrosome metabolism, Epistasis, Genetic, Inheritance Patterns, Microcephaly genetics, Nerve Tissue Proteins genetics
- Abstract
Recessive mutations in WD repeat domain 62 (WDR62) cause microcephaly and a wide spectrum of severe brain malformations. Disruption of the mouse ortholog results in microcephaly underlain by reduced proliferation of neocortical progenitors during late neurogenesis, abnormalities in asymmetric centrosome inheritance leading to neuronal migration delays, and altered neuronal differentiation. Spindle pole localization of WDR62 and mitotic progression are defective in patient-derived fibroblasts, which, similar to mouse neocortical progenitors, transiently arrest at prometaphase. Expression of WDR62 is closely correlated with components of the chromosome passenger complex (CPC), a key regulator of mitosis. Wild type WDR62, but not disease-associated mutant forms, interacts with the CPC core enzyme Aurora kinase B and staining of CPC components at centromeres is altered in patient-derived fibroblasts. Our findings demonstrate critical and diverse functions of WDR62 in neocortical development and provide insight into the mechanisms by which its disruption leads to a plethora of structural abnormalities.
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- 2017
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46. Corrigendum: A novel mutation in EED associated with overgrowth.
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Cohen AS, Tuysuz B, Shen Y, Bhalla SK, Jones SJ, and Gibson WT
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- 2017
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47. Measurement and mapping of the GSM-based electromagnetic pollution in the Black Sea region of Turkey.
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Tuysuz B and Mahmutoglu Y
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- Black Sea, Environmental Pollution analysis, Turkey, Electromagnetic Radiation, Environmental Pollution adverse effects, Radiation Monitoring standards, Telecommunications standards
- Abstract
Electromagnetic pollution caused by mobile communication devices, a new form of environmental pollution, has been one of the most concerning problems to date. Consequences of long-term exposure to the electromagnetic radiation caused by cell phone towers are still unknown and can potentially be a new health hazard. It is important to measure, analyze and map the electromagnetic radiation levels periodically because of the potential risks. The electromagnetic pollution maps can be used for the detection of diseases caused by the radiation. With the help of the radiation maps of different regions, comparative analysis can be provided and distribution of the diseases can be investigated. In this article, Global System for Mobile communication (GSM)-based electromagnetic pollution map of the Rize Providence, which has high cancer rates because of the Chernobyl nuclear explosion, is generated. First, locations of the GSM base stations are identified and according to the antenna types of the base stations, safety distances are determined. Subsequently, 155 measurements are taken during November 2014 from the nearest living quarters of the Rize city center in Turkey. The measurements are then assessed statistically. Thenceforth, for visual judgment of the determined statistics, collected measurements are presented on the map. It is observed that national limits are not exceeded, but it is also discovered that the safety distance is waived at some of the measurement points and above the average radiation levels are noted. Even if the national limits are not exceeded, the long-term effects of the exposition to the electromagnetic radiation can cause serious health problems.
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- 2017
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48. Natural History of Congenital Generalized Lipodystrophy: A Nationwide Study From Turkey.
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Akinci B, Onay H, Demir T, Ozen S, Kayserili H, Akinci G, Nur B, Tuysuz B, Nuri Ozbek M, Gungor A, Yildirim Simsir I, Altay C, Demir L, Simsek E, Atmaca M, Topaloglu H, Bilen H, Atmaca H, Atik T, Cavdar U, Altunoglu U, Aslanger A, Mihci E, Secil M, Saygili F, Comlekci A, and Garg A
- Subjects
- Acyltransferases genetics, Adolescent, Adult, Case-Control Studies, Child, Child, Preschool, DNA Mutational Analysis, Disease Progression, Female, GTP-Binding Protein gamma Subunits genetics, Humans, Infant, Insulin Resistance, Lipodystrophy, Congenital Generalized complications, Lipodystrophy, Congenital Generalized diagnosis, Lipodystrophy, Congenital Generalized genetics, Magnetic Resonance Imaging, Male, Middle Aged, Prognosis, Turkey, Young Adult, Lipodystrophy, Congenital Generalized pathology
- Abstract
Context: Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near-total lack of body fat., Objective: We aimed to study natural history and disease burden of various subtypes of CGL., Design: We attempted to ascertain nearly all patients with CGL in Turkey., Setting: This was a nationwide study., Patients or Other Participants: Participants included 33 patients (22 families) with CGL and 30 healthy controls., Main Outcome Measure(s): We wanted to ascertain genotypes by sequencing of the known genes. Whole-body magnetic resonance imaging was used to investigate the extent of fat loss. Metabolic abnormalities and end-organ complications were measured on prospective follow-up., Results: Analysis of the AGPAT2 gene revealed four previously reported and four novel mutations (CGL1; c.144C>A, c.667_705delinsCTGCG, c.268delC, and c.316+1G>T). Analysis of the BSCL2 gene revealed four different homozygous and one compound heterozygous possible disease-causing mutations (CGL2), including four novel mutations (c.280C>T, c.631delG, c.62A>T, and c.465-468delGACT). Two homozygous PTRF mutations (c.481-482insGTGA and c.259C>T) were identified (CGL4). Patients with CGL1 had preservation of adipose tissue in the palms, soles, scalp, and orbital region, and had relatively lower serum adiponectin levels as compared to CGL2 patients. CGL4 patients had myopathy and other distinct clinical features. All patients developed various metabolic abnormalities associated with insulin resistance. Hepatic involvement was more severe in CGL2. End-organ complications were observed at young ages. Two patients died at age 62 years from cardiovascular events., Conclusions: CGL patients from Turkey had both previously reported and novel mutations of the AGPAT2, BSCL2, and PTRF genes. Our study highlights the early onset of severe metabolic abnormalities and increased risk of end-organ complications in patients with CGL.
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- 2016
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49. Molecular etiology of arthrogryposis in multiple families of mostly Turkish origin.
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Bayram Y, Karaca E, Coban Akdemir Z, Yilmaz EO, Tayfun GA, Aydin H, Torun D, Bozdogan ST, Gezdirici A, Isikay S, Atik MM, Gambin T, Harel T, El-Hattab AW, Charng WL, Pehlivan D, Jhangiani SN, Muzny DM, Karaman A, Celik T, Yuregir OO, Yildirim T, Bayhan IA, Boerwinkle E, Gibbs RA, Elcioglu N, Tuysuz B, and Lupski JR
- Subjects
- Arthrogryposis pathology, Female, Genome-Wide Association Study, Humans, Male, Turkey, Arthrogryposis genetics, Exome, Family
- Abstract
Background: Arthrogryposis, defined as congenital joint contractures in 2 or more body areas, is a clinical sign rather than a specific disease diagnosis. To date, more than 400 different disorders have been described that present with arthrogryposis, and variants of more than 220 genes have been associated with these disorders; however, the underlying molecular etiology remains unknown in the considerable majority of these cases., Methods: We performed whole exome sequencing (WES) of 52 patients with clinical presentation of arthrogryposis from 48 different families., Results: Affected individuals from 17 families (35.4%) had variants in known arthrogryposis-associated genes, including homozygous variants of cholinergic γ nicotinic receptor (CHRNG, 6 subjects) and endothelin converting enzyme-like 1 (ECEL1, 4 subjects). Deleterious variants in candidate arthrogryposis-causing genes (fibrillin 3 [FBN3], myosin IXA [MYO9A], and pleckstrin and Sec7 domain containing 3 [PSD3]) were identified in 3 families (6.2%). Moreover, in 8 families with a homozygous mutation in an arthrogryposis-associated gene, we identified a second locus with either a homozygous or compound heterozygous variant in a candidate gene (myosin binding protein C, fast type [MYBPC2] and vacuolar protein sorting 8 [VPS8], 2 families, 4.2%) or in another disease-associated genes (6 families, 12.5%), indicating a potential mutational burden contributing to disease expression., Conclusion: In 58.3% of families, the arthrogryposis manifestation could be explained by a molecular diagnosis; however, the molecular etiology in subjects from 20 families remained unsolved by WES. Only 5 of these 20 unrelated subjects had a clinical presentation consistent with amyoplasia; a phenotype not thought to be of genetic origin. Our results indicate that increased use of genome-wide technologies will provide opportunities to better understand genetic models for diseases and molecular mechanisms of genetically heterogeneous disorders, such as arthrogryposis., Funding: This work was supported in part by US National Human Genome Research Institute (NHGRI)/National Heart, Lung, and Blood Institute (NHLBI) grant U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics, and US National Institute of Neurological Disorders and Stroke (NINDS) grant R01NS058529 to J.R. Lupski.
- Published
- 2016
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50. Phenotypic Expansion of Congenital Disorder of Glycosylation Due to SRD5A3 Null Mutation.
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Tuysuz B, Pehlivan D, Özkök A, Jhangiani S, Yalcinkaya C, Zeybek ÇA, Muzny DM, Lupski JR, Gibbs R, and Jaeken J
- Abstract
We present a boy, admitted at 4 months, with facial dysmorphism, hypertrichosis, loose skin, bilateral inguinal hernia, severe hypotonia, psychomotor disability, seizures with hypsarrhythmia (West syndrome), hepatosplenomegaly, increased serum transaminases, iris coloboma, glaucoma, corneal clouding and bilateral dilated lateral ventricles, and extra-axial post-cerebellar space. Serum transferrin isoelectrofocusing (IEF) showed a type 1 pattern. Whole-exome genotyping showed a previously reported homozygous nonsense mutation c.320G>A; p.Trp107X in SRD5A3. Epilepsy and glaucoma have been reported only once in the 19 described SRD5A3-congenital glycosylation defect patients, and corneal clouding not at all.
- Published
- 2016
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