Researcher:
Altunoğlu, Umut

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Umut

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Altunoğlu

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Altunoğlu, Umut

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Now showing 1 - 10 of 37
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    Publication
    Variant characterisation and clinical profile in a large cohort of patients with Ellis-van Creveld syndrome and a family with Weyers acrofacial dysostosis
    (BMJ Publishing Group, 2024) Palencia-Campos, Adrian; Guenes, Nilay; Turgut, Gozde Tutku; Nevado, Julian; Lapunzina, Pablo; Valencia, Maria; Iturrate, Asier; Otaify, Ghada; Elhossini, Rasha; Ashour, Adel; K. Amin, Asmaa; Elnahas, Rania F.; Fernandez-Nunez, Elisa; Flores, Carmen-Lisset; Arias, Pedro; Tenorio, Jair; Chamorro Fernandez, Carlos Israel; Guven, Yeliz; Ozsu, Elif; Eklioglu, Beray Selver; Ibarra-Ramirez, Marisol; Diness, Birgitte Rode; Burnyte, Birute; Ajmi, Houda; Yuksel, Zafer; Yildirim, Ruken; Unal, Edip; Abdalla, Ebtesam; Aglan, Mona; Tuysuz, Beyhan; Ruiz-Perez, Victor; Altunoğlu, Umut; Kayserili, Hülya; School of Medicine
    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.
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    DISP1 deficiency: Monoallelic and biallelic variants cause a spectrum of midline craniofacial malformations
    (Elsevier, 2024) Lavillaureix, Alinoë; Rollier, Paul; Kim, Artem; Panasenkava, Veranika; De Tayrac, Marie; Carré, Wilfrid; Guyodo, Hélène; Faoucher, Marie; Poirel, Elisabeth; Akloul, Linda; Quélin, Chloé; Whalen, Sandra; Bos, Jessica; Broekema, Marjoleine; van Hagen, Johanna M.; Grand, Katheryn; Allen-Sharpley, Michelle; Magness, Emily; McLean, Scott D.; En Qi Chong, Angie; Xue, Shifeng; Jeanne, Médéric; Almontashiri, Naif; Habhab, Wisam; Vanlerberghe, Clemence; Faivre, Laurence; Viora-Dupont, Eléonore; Philippe, Christophe; Safraou, Hana; Laffargue, Fanny; Mittendorf, Luisa; Abou Jamra, Rami; Patil, Siddaramappa Jagdish; Dalal, Ashwin; Sarma, Asodu Sandeep; Keren, Boris; Dubourg, Christèle; Odent, Sylvie; Dupé, Valérie; Kayserili, Hülya; Altunoğlu, Umut; Reversade, Bruno; School of Medicine
    Purpose: DISP1 encodes a transmembrane protein that regulates the secretion of the morphogen, Sonic hedgehog, a deficiency of which is a major cause of holoprosencephaly (HPE). This disorder covers a spectrum of brain and midline craniofacial malformations. The objective of the present study was to better delineate the clinical phenotypes associated with division transporter dispatched-1 (DISP1) variants. Methods: This study was based on the identification of at least 1 pathogenic variant of the DISP1 gene in individuals for whom detailed clinical data were available. Results: A total of 23 DISP1 variants were identified in heterozygous, compound heterozygous or homozygous states in 25 individuals with midline craniofacial defects. Most cases were minor forms of HPE, with craniofacial features such as orofacial cleft, solitary median maxillary central incisor, and congenital nasal pyriform aperture stenosis. These individuals had either monoallelic loss-of-function variants or biallelic missense variants in DISP1. In individuals with severe HPE, the DISP1 variants were commonly found associated with a variant in another HPE-linked gene (ie, oligogenic inheritance). Conclusion: The genetic findings we have acquired demonstrate a significant involvement of DISP1 variants in the phenotypic spectrum of midline defects. This underlines its importance as a crucial element in the efficient secretion of Sonic hedgehog. We also demonstrated that the very rare solitary median maxillary central incisor and congenital nasal pyriform aperture stenosis combination is part of the DISP1-related phenotype. The present study highlights the clinical risks to be flagged up during genetic counseling after the discovery of a pathogenic DISP1 variant.
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    Association of antenatal evaluations with postmortem and genetic findings in the series of fetal osteogenesis imperfecta
    (KARGER, 2024) Şentürk, Leyli; Güleç, Çağrı; Saraç Sivrikoz, Tuğba; Kalelioğlu, İbrahim Halil; Has, Recep; Coucke, Paul; Kalaycı, Tuğba; Wollnik, Bernd; Karaman, Birsen; Toksoy, Güven; Symoens, Sofie; Yiğit, Gökhan; Yüksel, Atıl; Başaran, Seher; Tüysüz, Beyhan; Uyguner, Zehra Oya; Kayserili, Hülya; Avcı, Şahin; Altunoğlu, Umut; School of Medicine; Koç University Hospital
    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.
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    Oculo-auricular syndrome in a new multiplex family does not link to HMX1 or its downstream enhancer
    (Springernature, 2024) Bertoli-Avella, Aida; Altunoğlu, Umut; Kaya, Mert; Satkın, Nihan Bilge; Börklü Yücel, Esra; Graduate School of Health Sciences; School of Medicine; Koç University Hospital
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    Recessive mutations in SCNM1 are a new cause of orofaciodigital syndrome due to errors in minor intron splicing affecting primary cilia
    (Springernature, 2024) Iturrate, Asier; Rivera-Barahona, Ana; Flores, Carmen-Lisset; Aotaify, Ghada; Elhossini, Rasha; Perez-Sanz, Marina L.; Nevado, Julian; Tenorio, Jair; Carlos Trivino, Juan; Garcia-Gonzalo, Francesc R.; Piceci-Sparascio, Francesca; De Luca, Alessandro; Martinez, Leopoldo; Kalayci, Tugba; Lapunzina, Pablo; Aglan, Mona; Abdalla, Ebtesam; Ruiz-Perez, Victor; Altunoğlu, Umut; School of Medicine
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    Undiagnosed arthrogryposis: further expanding the molecular and phenotypic spectrum
    (Springernature, 2023) Turgut, G. Tutku; Sarac-Sivrikoz, Tugba; Kalayci, Tugba; Toksoy, Guven; Karaman, Birsen; Gulec, Cagri; Sayin, Gozde Yesil; Basaran, Seher; Uyguner, Zehra Oya; Altunoğlu, Umut; Avcı, Şahin; Kayserili, Hülya; School of Medicine; Koç University Hospital
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    Investigation of genes responsible for diaphragmatic developmental defects with next generation sequencing technologies
    (Springernature, 2024) Heidargholizadeh, Somayyeh; Gulec, Cagri; Bulut, Gulnihal; Turgut, Gozde Tutku; Basaran, Seher; Karaman, Birsen; Altunoğlu, Umut; School of Medicine
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    Identification of germline variants in 546 breast/ ovarian cancer families: complementary testing with multigene NGS and MLPA panels
    (Springernature, 2024) Celik, Levent; Karanlik, Hasan; Atalay, Can; Kaban, Kerim; Igci, Abdullah; Saraçoğlu, Hilal Pırıl; Börklü Yücel, Esra; Altunoğlu, Umut; Selçukbiricik, Fatih; Ertürk, Kayhan; Vatansever, Doğan; Laçin, Şahin; Tunalı, Didem; Avcı, Şahin; Ağcaoğlu, Orhan; Dilege, Ece; Taşkıran, Çağatay; Mandel, Nil Molinas; Kayserili, Hülya; Eraslan, Serpil; Graduate School of Health Sciences; School of Medicine; Koç University Hospital
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    Comprehensive genetic testing in a cohort of 67 unrelated retinal dystrophy patients of Turkish and Eastern European descent
    (Springernature, 2024) Arf, Serra; Muslubas, Isil Sayman; Hocaoglu, Mumin; Karacorlu, Murat; Çepni, Ece; Altunoğlu, Umut; Börklü Yücel, Esra; Avcı, Şahin; Hasanreisoğlu, Murat; Kayserili, Hülya; Graduate School of Health Sciences; School of Medicine; Koç University Hospital
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    Homozygous NRP1 truncating variant in a multiplex family with conotruncal heart defects, lymphatic malformations and genitourinary anomalies
    (Springernature, 2023) Kalayci, Tugba; Uyguner, Zehra Oya; Altunoğlu, Umut; Kaya, Mert; School of Medicine; Graduate School of Health Sciences