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Publication Metadata only 268th ENMC workshop - Genetic diagnosis, clinical classification, outcome measures, and biomarkers in Facioscapulohumeral Muscular Dystrophy (FSHD): Relevance for clinical trials(Elsevier B.V., 2023) Montagnese F, de Valle K, Lemmers RJLF, Mul K, Dumonceaux J, Voermans N; 268th ENMC workshop participants.; Oflazer, Piraye; ; School of Medicine;Highlights This ENMC workshop has seen the participation of many important stakeholders working together to improve trial readiness in FSHD: patients and patients’ organizations (FSHD-Europe, FSHD-Society and FSHD Global), neuromuscular clinicians, geneticists, basic researchers, representatives of the TREAT-NMD network, the FSHD-CTRN and EMA. COMs represent useful tools for the standardized collection of clinical features but need to be selected to match the clinical setting of use. For patient care, they need to be informative, with practical and time efficient utility so as not to detract from clinical care. For clinical trial purposes, the need to be reliable, valid, meaningful and sensitive to change to better depict therapeutic responses. An optimized clinical evaluation and genetic test form is one of the goals of WG1 and 2. A diagnostic flowchart for FSHD1 and FSHD2 has been proposed. Another important unmet need for clinical trial readiness in FSHD is the identification of good therapeutic biomarkers, which ideally should be quantitative, non-invasive, applicable across the entire range of disease severity, sensitive to change, reliable and clinically meaningful. The WG 3 will produce standard operating procedures (SOPs) for DUX4 detection. Similarly, large differences in the reporting of studies performed on animal models, thus hindering interpretation, repeatability and comparison of the results need to be addressed. Guidelines regarding minimum information for publication of work including animal models for FSHD will therefore be published.Publication Metadata only A 52-year-old man with progressive weakness and incontinence(Sage, 2022) Danyeli, Ayca Ersen; Bozkurt, Subutay Berke; Uysal, Sanem Pinar; Akpek, Sergin; Kahyaoglu, Bulent; Peker, Selcuk; Altıntaş, Ayşe; Aygün, Murat Serhat; Akay, Olga Meltem; Üre, Ümit Barbaros; Ferhanoğlu, Ahmet Burhan; Faculty Member; Teaching Faculty; Faculty Member; Faculty Member; Faculty Member; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; 11611; 291692; 170966; N/A; 18320Here we report a challenging case of a 52-year-old man presenting with subacute constipation, urinary retention, impotence, absent Achilles reflexes, and hypoesthesia in S2-S5 dermatomes. We review the clinical decision-making as the symptoms evolved and diagnostic testing changed over time. Once the diagnosis is settled, we discuss the sign and symptoms, additional diagnostic tools, treatment options and prognosis.Publication Metadata only A biallelic mutation links myorg to autosomal-recessive primary familial brain calcification(Oxford University Press (OUP), 2019) Forouhideh, Yalda; Mueller, Kathrin; Ruf, Wolfgang; Assi, Muhannad; Seker, Tuncay; Knehr, Antje; Strom, Tim M.; Gorges, Martin; Schradt, Falk; Meitinger, Thomas; Ludolph, Albert C.; Pinkhardt, Elmar H.; Kassubek, Jan; Uttner, Ingo; Weishaupt, Jochen H.; N/A; Tunca, Ceren; Başak, Ayşe Nazlı; Researcher; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; School of Medicine; N/A; 1512N/APublication Metadata only A case of drop foot due to piriformis syndrome(Springer Heidelberg, 2015) Yıldırım, Pelin; Güler, Tuba; Özer, Tülay; Gündüz, Osman Hakan; N/A; Mısırlıoğlu, Tuğçe Özekli; Doctor; N/A; Koç University Hospital; 175999N/APublication Metadata only A case with new-onset neuromyelitis optica spectrum disorder following COVID-19 mRNA BNT162b2 vaccination(Lippincott Williams & Wilkins, 2022) Afşar, Nazire; N/A; N/A; N/A; Çalışkan, İlay; Buluş, Eser; Polat-Altıntaş, Sevgi; Master Student; Doctor; Researcher; N/A; N/A; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; N/A; N/A; 150017Introduction: In the midst of the coronavirus disease of 2019 pandemic, active immunization by effective vaccination gained utmost importance in terms of global health. The messenger RNA (mRNA) vaccines are novel strategies requiring clinical surveillance for adverse events. Case Report: We report a 43-year-old previously healthy female with an optic neuritis attack 24 hours following immunization with the second dose of coronavirus disease of 2019 mRNA BNT162b2 vaccine. A second transverse myelitis attack together with an elevated anti-AQP-4 antibody titer confirmed the diagnosis of neuromyelitis optica spectrum disorder. Conclusion: Our case identifies the BNT162b2 vaccine as a possible trigger for neuromyelitis optica spectrum disorder. This rare and potentially coincidental event has no implications for vaccine administration practices. However, further research is needed to elucidate the effects of mRNA vaccines on humoral and cell-mediated immunity.Publication Metadata only A case-control candidate gene study on base excision repair mechanism (BER) as a novel therapeutic target in bipolar disorder(Wiley, 2022) Ozerdem, Aysegul; Veldic, Marin; Singh, Balwinder; Frye, Mark; Schulze, Thomas; Biernacka, Joanna; Winham, Stacey J.; N/A; Ceylan, Deniz; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 137755N/APublication Metadata only A combined clinical and computational approach to understand the sod1a4t-mediated pathogenesis of rapidly progressive familial amyotrophic lateral sclerosis(Wiley, 2019) Gelener, P.; Diker, S.; Ergoren, M. C.; Terali, K.; Tan, E.; N/A; Başak, Ayşe Nazlı; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 1512Here, we aim to provide a comprehensive clinical and biomolecular description of familial amyotrophic lateral sclerosis (fALS) in a 25-year-old female patient with respect to the SOD1A4T genotype. The clinical diagnosis of the disease was based on family history, neurological examination, electroneurophysiological studies, and revised El Escorial criteria. The heterozygous presence of the A4T mutation in the proband was confrmed by PCR coupled with Sanger sequencing of exon 1 of the SOD1 gene. The mutation was introduced in silico into the three-dimensional structure of the native protein. After energy minimization and quality assessment, non-covalent interactions around threonine-4 and changes in protein stability were calculated computationally. The patient difered widely in age at onset, initial neurological symptoms and fndings, and survival time from her kindred, in which several members are afected. SOD1A4T-linked fALS in this case had bulbar involvement at onset, a combination of lower and upper motor neuron signs and showed rapid progression. Unlike alanine-4, threonine-4 failed to engage in hydrophobic interactions with the vicinal non-polar amino acids. The overall fold of the modeled SOD1A4T mutant remained intact, but unfolding free energy estimations disclosed a decrease in the protein’s stability. We report a phenotypically distinct patient with fALS due to the SOD1A4T mutation and further expand the largest pedigree ever published for SOD1A4T-linked fALS. Genotype‒phenotype correlation in fALS is complex, and it demands detailed clinical investigation and advanced scientifc research. Awareness of the broadened phenotypic spectrum might potentially enhance the diagnosis and genetic counseling of fALS.Publication Metadata only A family from Turkey with congenital myasthenia and hereditary(Wiley, 2023) Tezen, D.; Gündüz, A.; Demirbilek, V.; Khojakulov, Zakhiriddin; Başak, Ayşe Nazlı; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of MedicinePublication Metadata only A genetic cause for intractable seizures: atypical Gaucher disease with a novel pathological variant(WILEY, 2024) Üçem, Selen; Avcı, Şahin; Gürses, Rabia Candan; School of Medicine; Koç University HospitalPublication Metadata only A multi-centre longitudinal study analysing multiple sclerosis disease-modifying therapy prescribing patterns during the Covid-19 pandemic(Springer Science and Business Media Deutschland GmbH, 2024) Lal, Anoushka P.; Foong, Yi Chao; Sanfilippo, Paul G.; Spelman, Tim; Rath, Louise; Levitz, David; Fabis-Pedrini, Marzena; Foschi, Matteo; Habek, Mario; Kalincik, Tomas; Roos, Izanne; Lechner-Scott, Jeannette; John, Nevin; Soysal, Aysun; D’Amico, Emanuele; Gouider, Riadh; Mrabet, Saloua; Gross-Paju, Katrin; Cárdenas-Robledo, Simón; Moghadasi, Abdorreza Naser; Sa, Maria Jose; Gray, Orla; Oh, Jiwon; Reddel, Stephen; Ramanathan, Sudarshini; Al-Harbi, Talal; Hardy, Todd A.; Ozakbas, Serkan; Alroughani, Raed; Kermode, Allan G.; Surcinelli, Andrea; Laureys, Guy; Eichau, Sara; Prat, Alexandre; Girard, Marc; Duquette, Pierre; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Maimone, Davide; McCombe, Pamela; Spitaleri, Daniele; Sanchez-Menoyo, Jose Luis; Yetkin, Mehmet Fatih; Baghbanian, Seyed Mohammad; Karabudak, Rana; Al-Asmi, Abdullah; Jakob, Gregor Brecl; Khoury, Samia J.; Etemadifar, Masoud; van Pesch, Vincent; Buzzard, Katherine; Taylor, Bruce; Butzkueven, Helmut; Van der Walt, Anneke; Altıntaş, Ayşe; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of MedicineBackground: The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset. Methods: A multi-centre longitudinal study with 8,771 participants from MSBase was conducted. Two time periods were defined: pre-pandemic (March 11 2018–March 10 2020) and post-pandemic onset (March 11 2020–11 March 2022). The association between time and prescribing trends was analysed using multivariable mixed-effects logistic regression. DMT initiation refers to first initiation of any DMT, whilst DMT switches indicate changing regimen within 6 months of last use. Results: Post-pandemic onset, there was a significant increase in DMT initiation/switching to natalizumab and cladribine [(Natalizumab-initiation: OR 1.72, 95% CI 1.39–2.13;switching: OR 1.66, 95% CI 1.40–1.98), (Cladribine-initiation: OR 1.43, 95% CI 1.09–1.87;switching: OR 1.67, 95% CI 1.41–1.98)]. Anti-CD20mAb initiation/switching decreased in the year of the pandemic, but recovered in the second year, such that overall odds increased slightly post-pandemic (initiation: OR 1.26, 95% CI 1.06–1.49;Switching: OR 1.15, 95% CI 1.02–1.29. Initiation/switching of fingolimod, interferon-beta, and alemtuzumab significantly decreased [(Fingolimod-initiation: OR 0.55, 95% CI 0.41–0.73;switching: OR 0.49, 95% CI 0.41–0.58), (Interferon-gamma-initiation: OR 0.48, 95% CI 0.41–0.57;switching: OR 0.78, 95% CI 0.62–0.99), (Alemtuzumab-initiation: OR 0.27, 95% CI 0.15–0.48;switching: OR 0.27, 95% CI 0.17–0.44)]. Conclusions: Post-pandemic onset, clinicians preferentially prescribed natalizumab and cladribine over anti-CD20 mAbs and fingolimod, likely to preserve efficacy but reduce perceived immunosuppressive risks. This could have implications for disease progression in pwMS. Our findings highlight the significance of equitable DMT access globally, and the importance of evidence-based decision-making in global health challenges. © The Author(s) 2024.