Article
Endocrinology & Metabolism
Jenifer P. Suntharalingham, Miho Ishida, Ignacio Del Valle, Susanne E. Stalman, Nita Solanky, Emma Wakeling, Gudrun E. Moore, John C. Achermann, Federica Buonocore
Summary: Heterozygous de novo variants in SAMD9 cause MIRAGE syndrome, involving multiple systems such as growth restriction, adrenal dysfunction, and reproductive phenotypic abnormalities. Some children may present with isolated myelodysplastic syndrome without MIRAGE features.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Dermatology
P. H. Hoeger
Summary: Vascular malformations are caused by localized defects in vascular development and are influenced by various factors, leading to complex genotype-phenotype correlations. The differential diagnosis of VM is challenging, except for diseases with pathognomonic phenotypes, but increasing sequencing techniques will facilitate this process. Targeted pharmacotherapy shows promise for the treatment of VM patients.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
(2021)
Article
Multidisciplinary Sciences
Aritro Nath, Patrick A. Cosgrove, Hoda Mirsafian, Elizabeth L. Christie, Lance Pflieger, Benjamin Copeland, Sumana Majumdar, Mihaela C. Cristea, Ernest S. Han, Stephen J. Lee, Edward W. Wang, Sian Fereday, Nadia Traficante, Ravi Salgia, Theresa Werner, Adam L. Cohen, Philip Moos, Jeffrey T. Chang, David D. L. Bowtell, Andrea H. Bild
Summary: The study reveals the core archetypes in progressive HGSOC and demonstrates consistent enrichment of subclones with the metabolism and proliferation archetype as resistance is acquired to multiple lines of therapy. The shifts in metabolism and proliferation are associated with treatment response and clonal heterogeneity in HGSOC.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Emma M. Groarke, Bhavisha A. Patel, Ruba Shalhoub, Fernanda Gutierrez-Rodrigues, Parth Desai, Harshraj Leuva, Yoshitaka Zaimoku, Casey Paton, Nina Spitofsky, Jennifer Lotter, Olga Rios, Richard W. Childs, David J. Young, Alina Dulau-Florea, Cynthia E. Dunbar, Katherine R. Calvo, Colin O. Wu, Neal S. Young
Summary: This study assessed predictors, genetic characteristics, and long-term outcomes of patients with severe aplastic anemia (SAA) who experienced clonal evolution after immunosuppressive therapy (IST). High-risk evolution was associated with older age and higher ANC levels. Patients with high-risk clonal evolution had lower overall survival rates, but those who underwent hematopoietic stem cell transplant (HSCT) showed improved survival. Certain gene mutations detected at 6 months after IST were predictive of high-risk evolution.
Article
Clinical Neurology
Maria Cristina Cioclu, Ilaria Mosca, Paolo Ambrosino, Deborah Puzo, Allan Bayat, Saskia B. Wortmann, Johannes Koch, Vincent Strehlow, Kentaro Shirai, Naomichi Matsumoto, Stephan J. Sanders, Vincent Michaud, Marine Legendre, Antonella Riva, Pasquale Striano, Hiltrud Muhle, Manuela Pendziwiat, Gaetan Lesca, Giuseppe Donato Mangano, Rosaria Nardello, Johannes R. Lemke, Rikke S. Moller, Maria Virginia Soldovieri, Guido Rubboli, Maurizio Taglialatela
Summary: This study describes the phenotypic and genetic features of patients with KCNT2-related developmental epileptic encephalopathy (DEE), and investigates the functional and pharmacological properties of KCNT2 channels carrying novel or previously untested variants. The results expand the phenotypic and genotypic spectrum of KCNT2-related disorders, and highlight the need for targeted therapies based on the molecular phenotype.
ANNALS OF NEUROLOGY
(2023)
Editorial Material
Hematology
Laura G. Schuettpelz
Summary: In this study published in Blood, Tsaknakis and colleagues used targeted next-generation sequencing to determine the frequency and clinical significance of clonal hematopoiesis in a cohort of 185 patients with chronic idiopathic neutropenia.
Article
Multidisciplinary Sciences
Amanda M. Smith, Taylor A. LaValle, Marwan Shinawi, Sai M. Ramakrishnan, Haley J. Abel, Cheryl A. Hill, Nicole M. Kirkland, Michael P. Rettig, Nichole M. Helton, Sharon E. Heath, Francesca Ferraro, David Y. Chen, Sangeeta Adak, Clay F. Semenkovich, Diana L. Christian, Jenna R. Martin, Harrison W. Gabel, Christopher A. Miller, Timothy J. Ley
Summary: Germline pathogenic variants in DNMT3A can lead to overgrowth syndrome, with behavioral and hematopoietic phenotypes. Using a mouse model, researchers found that this mutation may be associated with alterations in DNA methylation.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Sushree S. Sahoo, Victor B. Pastor, Charnise Goodings, Rebecca K. Voss, Emilia J. Kozyra, Amina Szvetnik, Peter Noellke, Michael Dworzak, Jan Stary, Franco Locatelli, Riccardo Masetti, Markus Schmugge, Barbara De Moerloose, Albert Catala, Krisztian Kallay, Dominik Turkiewicz, Henrik Hasle, Jochen Buechner, Kirsi Jahnukainen, Marek Ussowicz, Sophia Polychronopoulou, Owen P. Smith, Oksana Fabri, Shlomit Barzilai, Valerie de Haas, Irith Baumann, Stephan Schwarz-Furlan, Marena R. Niewisch, Martin G. Sauer, Birgit Burkhardt, Peter Lang, Peter Bader, Rita Beier, Ingo Mueller, Michael H. Albert, Roland Meisel, Ansgar Schulz, Gunnar Cario, Pritam K. Panda, Julius Wehrle, Shinsuke Hirabayashi, Marta Derecka, Robert Durruthy-Durruthy, Gudrun Goehring, Ayami Yoshimi-Noellke, Manching Ku, Dirk Lebrecht, Miriam Erlacher, Christian Flotho, Brigitte Strahm, Charlotte M. Niemeyer, Marcin W. Wlodarski
Summary: This study provides insights into the genetic determinants of disease progression and clinical outcomes in individuals with myelodysplastic syndromes, particularly those with SAMD9 and SAMD9L mutations. The findings suggest that somatic genetic rescue is common in SAMD9/9L(mut) MDS, showcasing the exceptional plasticity of hematopoiesis in children.
Article
Multidisciplinary Sciences
Kuan-lin Huang, Adam D. Scott, Daniel Cui Zhou, Liang-Bo Wang, Amila Weerasinghe, Abdulkadir Elmas, Ruiyang Liu, Yige Wu, Michael C. Wendl, Matthew A. Wyczalkowski, Jessika Baral, Sohini Sengupta, Chin-Wen Lai, Kelly Ruggles, Samuel H. Payne, Benjamin Raphael, David Fenyo, Ken Chen, Gordon Mills, Li Ding
Summary: Advances in mass-spectrometry have led to the generation of large-scale proteomics datasets containing tens of thousands of phosphorylation sites. Using a bioinformatics tool called HotPho, researchers identified 474 hybrid clusters of phosphosites and cancer mutations on protein structures, highlighting nearly 3,000 likely functional mutations and over 1,000 cancer phosphosites for potential clinical relevance.
NATURE COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Akiko Nagamachi, Akinori Kanai, Megumi Nakamura, Hiroshi Okuda, Akihiko Yokoyama, Satoru Shinriki, Hirotaka Matsui, Toshiya Inaba
Summary: Samd9/9L syndromes are a group of inherited bone marrow failure syndromes that are caused by gain-of-function mutations in the genes located on chromosome 7. These syndromes often lead to infantile myelodysplastic syndromes associated with monosomy 7, characterized by bone marrow failure and multiorgan degeneration.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Lorenz M. Bell, Annegret Holm, Uta Matysiak, Wolfgang Driever, Jochen Roessler, Denny Schanze, Ilse Wieland, Charlotte M. Niemeyer, Martin Zenker, Friedrich G. Kapp
Summary: This study investigates the pathogenic factors of vascular malformations, the impact of mutations on the type of malformation, and the use of a zebrafish model for evaluating pathogenicity of mutations and testing candidate drugs in a personalized and mutation-specific approach.
HUMAN MOLECULAR GENETICS
(2022)
Article
Multidisciplinary Sciences
Ali Reza Ebadi, Ali Soleimani, Abdulbaghi Ghaderzadeh
Summary: The study introduces a new method to extract driver genes more accurately through subspace learning and unsupervised learning, showing higher predictive accuracy. By comparing p-value overlap and new driver genes, the method outperforms in identifying driver genes in cancer tumors.
SCIENTIFIC REPORTS
(2021)
Article
Clinical Neurology
Michael Zech, Robert Kopajtich, Katja Steinbruecker, Celine Bris, Naig Gueguen, Rene G. Feichtinger, Melanie T. Achleitner, Neslihan Duzkale, Maximilien Perivier, Johannes Koch, Harald Engelhardt, Peter Freisinger, Matias Wagner, Theresa Brunet, Riccardo Berutti, Dmitrii Smirnov, Tharsini Navaratnarajah, Richard J. T. Rodenburg, Lynn S. Pais, Christina Austin-Tse, Melanie O'Leary, Sylvia Boesch, Robert Jech, Somayeh Bakhtiari, Sheng Chih Jin, Friederike Wilbert, Michael C. Kruer, Saskia B. Wortmann, Matthias Eckenweiler, Johannes A. Mayr, Felix Distelmaier, Robert Steinfeld, Juliane Winkelmann, Holger Prokisch
Summary: This study identified novel phenotypes associated with mutations in ATPase subunits, expanding the understanding of ATPase-related diseases. The clinical manifestations of patients with ATPase defects varied, ranging from mild hypotonia to severe epilepsy and developmental delays. Dystonia was a common feature in the affected individuals.
ANNALS OF NEUROLOGY
(2022)
Article
Neurosciences
Bofan Wu, Andrew P. Bagshaw, Clayton Hickey, Simone Kuehn, Martin Wilson
Summary: Advances in magnetic resonance imaging have revealed the relationship between individual differences in the structure and function of the human brain and health and cognition. However, the relationship between individual differences and neuro-metabolite levels remains largely unexplored. This study measured metabolite levels and achieved high classification accuracy using machine learning and metabolomic methodology. These findings suggest the existence of neuro-metabolic phenotypes that can be measured using widely available technology.
Article
Multidisciplinary Sciences
Benedith Oben, Guy Froyen, Kylee H. Maclachlan, Daniel Leongamornlert, Federico Abascal, Binbin Zheng-Lin, Venkata Yellapantula, Andriy Derkach, Ellen Geerdens, Benjamin T. Diamond, Ingrid Arijs, Brigitte Maes, Kimberly Vanhees, Malin Hultcrantz, Elisabet E. Manasanch, Dickran Kazandjian, Alexander Lesokhin, Ahmet Dogan, Yanming Zhang, Aneta Mikulasova, Brian Walker, Gareth Morgan, Peter J. Campbell, Ola Landgren, Jean-Luc Rummens, Niccolo Bolli, Francesco Maura
Summary: The study demonstrates that MGUS and SMM that do not progress to multiple myeloma have a distinct genomic profile and emerge later in the patient's life.
NATURE COMMUNICATIONS
(2021)
Article
Endocrinology & Metabolism
Adina Sophie Graffunder, Sarah Paisdzior, Robert Opitz, Kostja Renko, Peter Kuehnen, Heike Biebermann
Summary: MCT8 is a crucial thyroid hormone transporter involved in fetal development. By introducing a TC-tag in the MCT8 protein, it is possible to monitor its expression in real time in cell culture models, potentially leading to the development of stable hiPSC MCT8 reporter lines for future studies.
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES
(2022)
Article
Computer Science, Interdisciplinary Applications
Ivan Phelan, Penny Jayne Furness, Maria Matsangidou, Alicia Carrion-Plaza, Heather Dunn, Paul Dimitri, Shirley A. Lindley
Summary: This study explores the feasibility of using virtual reality as a tool for therapeutic physiotherapy for child patients in an out-patient hospital department. The results show that virtual reality is an effective solution for children with upper limb motor impairment undergoing painful therapeutic process within a hospital environment. It can improve functional disabilities, alleviate perceived pain, reduce the perceived difficulty of rehabilitation exercises, increase exercise duration and produce positive emotions towards the therapy.
Letter
Radiology, Nuclear Medicine & Medical Imaging
Vikas Prasad, Marti Boss, Christof Rottenburger, Winfried Brenner, Oliver Blankenstein, Sonal Prasad, Mijke Buitinga, Pratik Shah, Martin Gotthardt
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Endocrinology & Metabolism
Jenifer P. Suntharalingham, Miho Ishida, Ignacio Del Valle, Susanne E. Stalman, Nita Solanky, Emma Wakeling, Gudrun E. Moore, John C. Achermann, Federica Buonocore
Summary: Heterozygous de novo variants in SAMD9 cause MIRAGE syndrome, involving multiple systems such as growth restriction, adrenal dysfunction, and reproductive phenotypic abnormalities. Some children may present with isolated myelodysplastic syndrome without MIRAGE features.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Rheumatology
Meredyth G. Ll Wilkinson, Dale Moulding, Thomas C. R. McDonnell, Michael Orford, Chris Wincup, Joanna Y. J. Ting, Georg W. Otto, Restuadi Restuadi, Daniel Kelberman, Charalampia Papadopoulou, Sergi Castellano, Simon Eaton, Claire T. Deakin, Elizabeth C. Rosser, Lucy R. Wedderburn
Summary: This study identifies a novel pathway in which altered mitochondrial biology in CD14+ monocytes of Juvenile dermatomyositis (JDM) patients leads to the production of oxidized mitochondrial DNA (oxmtDNA) and stimulates the expression of interferon (IFN) type 1 signature genes. Targeting this pathway has therapeutic potential in JDM and other IFN type 1-driven autoimmune diseases.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Meeting Abstract
Hematology
Masanori Yoshida, Felicia Andresen, Hermann Yang, Sara Lewis, Miriam Erlacher, Dirk Lebrecht, Akiko Shimamura, Charlotte M. Niemeyer, Sushree S. Sahoo, Marcin W. Wlodarski
Article
Computer Science, Interdisciplinary Applications
Ivan Phelan, Alicia Carrion-Plaza, Penny J. Furness, Paul Dimitri
Summary: Upper limb motor impairment (ULMI) rehabilitation using home-based immersive virtual reality (IVR) has been shown to be an effective and enjoyable method for children. This feasibility study found that IVR for ULMI home rehabilitation is easy to learn and acceptable, improves motor function, reduces difficulty in therapy reproduction, is motivating and enjoyable, and improves quality of life for children. It presents an innovative solution for home rehabilitation, particularly during the Covid-19 pandemic.
Letter
Biophysics
Luca Vinci, Christian Flotho, Peter Noellke, Dirk Lebrecht, Riccardo Masetti, Valerie de Haas, Barbara De Moerloose, Michael Dworzak, Henrik Hasle, Tayfun Guengoer, Jan Stary, Dominik Turkiewicz, Marek Ussowicz, Cristina Diaz de Heredia, Jochen Buechner, Kirsi Jahnukainen, Krisztian Kallay, Ivana Bodova, Owen P. P. Smith, Marco Zecca, Dorine Bresters, Peter Lang, Tania Nicole Masmas, Roland Meisel, Herbert Pichler, Miriam Erlacher, Gudrun Goehring, Franco Locatelli, Brigitte Strahm, Charlotte M. M. Niemeyer, Ayami Yoshimi
BONE MARROW TRANSPLANTATION
(2023)
Article
Genetics & Heredity
Alisa Foerster, Claudia Davenport, Nicolas Duployez, Miriam Erlacher, Alina Ferster, Jude Fitzgibbon, Gudrun Goehring, Henrik Hasle, Marjolijn C. Jongmans, Alexandra Kolenova, Geertruijte Kronnie, Tim Lammens, Cristina Mecucci, Wojciech Mlynarski, Charlotte M. Niemeyer, Francesc Sole, Tomasz Szczepanski, Esme Waanders, Andrea Biondi, Marcin Wlodarski, Brigitte Schlegelberger, Tim Ripperger
Summary: Hematologic malignancies are no longer considered sporadic and there is a need for increased awareness of familial cases. Individuals carrying a likely pathogenic germline variant are at an increased risk of developing hematologic malignancies. To ensure high-quality patient care, an European Standard Clinical Practice document has been proposed by an interdisciplinary team of experts to address key issues such as identification of individuals with familial leukemia, genetic analysis, counseling, surveillance, and support. The importance of natural history studies and registries for future evidence-based recommendations is emphasized.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2023)
Article
Cell Biology
Lara Lechner, Robert Opitz, Matt J. Silver, Philipp M. Krabusch, Andrew M. Prentice, Martha S. Field, Harald Stachelscheid, Elsa Leitao, Christopher Schroeder, Valeria Fernandez Vallone, Bernhard Horsthemke, Karl-Heinz Joeckel, Boerge Schmidt, Markus M. Noethen, Per Hoffmann, Stefan Herms, Patrick W. Kleyn, Matthias Megges, Ulrike Blume-Peytavi, Katja Weiss, Knut Mai, Oliver Blankenstein, Benedikt Obermayer, Susanna Wiegand, Peter Kuehnen
Summary: Increasing evidence suggests that epigenetic variants play a role in the development of obesity. The study identified POMC hypermethylation as a risk factor for obesity and found that it is not genetically determined. The researchers also established an embryonic stem cell model to investigate the early establishment of POMC methylation states.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Jenifer P. Suntharalingham, Miho Ishida, Antoinette Cameron-Pimblett, Sinead M. McGlacken-Byrne, Federica Buonocore, Ignacio del Valle, Gaganjit Kaur Madhan, Tony Brooks, Gerard S. Conway, John C. Achermann
Summary: This study aimed to investigate the global genetic variability in women with Turner syndrome (TS), whether common variants in X genes are associated with phenotype, and the replication of the association between autosomal TIMP3 variants and congenital cardiovascular anomalies (CCA). The results showed that there was no excess of genetic variability in women with TS, no obvious X-chromosome variants driving phenotype were found, but several possible genes/variants of interest emerged. Additionally, the association between autosomal TIMP3 variants and CCA was replicated.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Medicine, Research & Experimental
Ignacio del Valle, Matthew D. Young, Gerda Kildisiute, Olumide K. Ogunbiyi, Federica Buonocore, Ian C. Simcock, Eleonora Khabirova, Berta Crespo, Nadjeda Moreno, Tony Brooks, Paola Niola, Katherine Swarbrick, Jenifer P. Suntharalingham, Sinead M. McGlacken-Byrne, Owen J. Arthurs, Sam Behjati, John C. Achermann
Summary: By using various techniques including single-cell and bulk RNA sequencing, spatial transcriptomics, IHC, and micro-focus computed tomography, we investigated key aspects of adrenal development in the first 20 weeks of gestation. The study revealed rapid adrenal growth and vascularization, with more cell division in the outer definitive zone (DZ). Our findings provide insights into human adrenal development and have clinical implications for various adrenal disorders.
Article
Health Care Sciences & Services
Jose Labarta, Paul Dimitri, Matthew Keiser, Ekaterina Koledova, Octavio Rivera-Romero
Summary: This study evaluated the perspectives of healthcare professionals (HCPs) on the third generation of the easypod device (EP3) for the delivery of r-hGH treatment. HCPs reported that EP3 had significant improvements, such as a touch screen interface and real-time data transmission functionality. They also believed that EP3 should be part of a digital health ecosystem that provides complementary functionalities, including data analysis.
JMIR HUMAN FACTORS
(2023)
Article
Biochemical Research Methods
Katarzyna A. Ludwik, Narasimha Telugu, Sandra Schommer, Harald Stachelscheid, Sebastian Dieceke
Summary: CRISPR-Cas9 technology combined with human induced pluripotent stem cells enables precise disease modeling in pluripotent and specialized cells. This article presents an optimized CRISPR-Cas9 pipeline called ASSURED (affordable, successful, specific, user-friendly, rapid, efficient, and deliverable) for generating gene-modified single-cell-derived knockout or single-nucleotide-polymorphism-modified knockin hiPSC clones. The article describes the steps for analyzing targeted genomic sequences, designing guide RNAs and homology repair templates, as well as the CRISPR-Cas9 delivery workflow, efficiency evaluation, automated cell isolation, and clone screening.
Meeting Abstract
Rheumatology
Meredyth G. L. L. Wilkinson, Dale Moulding, Thomas C. R. McDonnell, Mi-Chael Orford, Chris Wincup, Joanna Ting, Georg Otto, Daniel Kelberman, Sergi Castellano, Simon Eaton, Claire T. Deakin, Elizabeth C. Rosser, Lucy R. Wedderburn
CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
(2023)