Article
Endocrinology & Metabolism
Sara Amaral, Ana Palha, Paula Bogalho, Jose Silva-Nunes
Summary: HNF1B-MODY, a rare subtype of diabetes, is often misdiagnosed as type 1 or type 2 diabetes. This study found that some patients with HNF1B-MODY presented with kidney malformations and chronic kidney disease, highlighting the importance of early diagnosis for minimizing complications and providing genetic counseling.
DIABETOLOGY & METABOLIC SYNDROME
(2023)
Article
Health Care Sciences & Services
Maja Baretic, Domagoj Caban, Jadranka Sertic
Summary: This study examined the clinical characteristics and gene mutations of Croatian patients, and identified new genetic and clinical aspects of HNF1B-related MODY.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Genetics & Heredity
Konstantina Patouni, Ondrej Cinek, Stepanka Pruhova, Lenka Elblova, Maria Xatzipsalti, Amalia Sertedaki, Andriani Vazeou
Summary: This case report describes a female patient with Maturity onset diabetes of the young (MODY) who carries pathogenic variants in both the HNF1A and HNF1B genes. The study suggests that digenic inheritance of MODY pathogenic variants may be more common than currently reported in literature, and the use of Next Generation Sequencing panels could help identify such cases that may otherwise remain undiagnosed.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2021)
Review
Cell Biology
Alessandro Gambella, Silvia Kalantari, Massimiliano Cadamuro, Marco Quaglia, Maurizio Delvecchio, Luca Fabris, Michele Pinon
Summary: The hepatocyte nuclear factor 1 beta (HNF1B) gene plays a crucial role in the development of specialized epithelia in various organs during embryogenesis. Pathogenic variants of HNF1B have been associated with a complex syndrome that mainly affects children, leading to diabetes and renal complications. However, recent studies have highlighted the importance of liver involvement, including a potential link to tumor development, expanding the understanding of HNF1B-associated disease. This review aims to provide a comprehensive analysis of the genetic, phenotypic, and clinical features of HNF1B deficiency in both pediatric and adult populations.
Article
Biology
Zsolt Gaal, Zsuzsanna Szucs, Iren Kantor, Andrea Luczay, Peter Toth-Heyn, Orsolya Benn, Eniko Felszeghy, Zsuzsanna Karadi, Laszlo Madar, Istvan Balogh
Summary: MODY is a genetically heterogeneous form of diabetes with about a dozen known causal genes, and treatment should be selected based on the specific gene mutation for each individual patient. The importance of genetic testing in diagnosing MODY and determining the subtype for personalized treatment is highlighted.
Article
Endocrinology & Metabolism
Youmna Francis, Clarisse Tiercelin, Laure Alexandre-Heyman, Etienne Larger, Daniele Dubois-Laforgue
Summary: This article presents a case of a 39-year-old female patient who was initially diagnosed with type 1 diabetes but later labeled as having atypical type 2 diabetes. She was finally recognized as having HNF1B-MODY, a diagnosis suggested by the absence of metabolic syndrome and presence of chronically disturbed liver function tests and hypomagnesemia. There was a 10-year delay between the onset of diabetes and the molecular diagnosis.
JOURNAL OF THE ENDOCRINE SOCIETY
(2022)
Article
Endocrinology & Metabolism
David T. Broome, Kevin M. Pantalone, Sangeeta R. Kashyap, Louis H. Philipson
Summary: Maturity-onset diabetes of the young (MODY) is a genetic form of diabetes that remains underdiagnosed. Diagnosis involves clinical presentation, family history, lab, and genetic testing. Treatment and monitoring depend on the identified variant.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Genetics & Heredity
Feifan Xiao, Xiuyun Liu, Yulan Lu, Bingbing Wu, Renchao Liu, Bo Liu, Kai Yan, Huiyao Chen, Guoqiang Cheng, Laishuan Wang, Qi Ni, Gang Li, Ping Zhang, Xiaomin Peng, Yun Cao, Chun Shen, Huijun Wang, Wenhao Zhou
Summary: Annular pancreas is a congenital anomaly that can cause acute abdominal pain and vomiting, and it may also be present in patients with 17q12 duplication. Common features of 17q12 duplication syndrome include intellectual disability, gross motor delay, and seizures. Zebrafish studies confirmed the role of the HNF1B gene in pancreatic development.
FRONTIERS IN GENETICS
(2021)
Review
Medicine, General & Internal
Alba Rojano-Toimil, Jesus Rivera-Esteban, Ramiro Manzano-Nunez, Juan Banares, David Martinez Selva, Pablo Gabriel-Medina, Roser Ferrer, Juan M. Pericas, Andreea Ciudin
Summary: Type 2 diabetes and non-alcoholic fatty liver disease have traditionally been linked, but recent studies suggest that fatty liver disease may also be common in other types of diabetes. However, screening for fatty liver disease is not yet implemented in daily care routine. Implementing a clinical algorithm based on a simple, non-invasive, cost-effective model would help identify high-risk patients and improve insulin resistance and high blood sugar levels through lifestyle changes, weight loss, and new drug therapies.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Endocrinology & Metabolism
S. Bonetti, C. Zusi, E. Rinaldi, M. L. Boselli, A. Csermely, G. Malerba, E. Trabetti, E. Bonora, R. C. Bonadonna, M. Trombetta
Summary: This study found that common genetic variability of monogenic diabetes genes is significantly associated with impaired beta-cell function in patients with newly diagnosed type 2 diabetes mellitus (T2DM), suggesting that these genes may be targeted by specific treatments for T2DM.
DIABETES & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Mei Guo, Qinqin Xu, Xuefeng Yu, Qin Yang, Shiying Shao
Summary: ADP is a rare disease associated with variants of the HNF1B gene, presenting with various symptoms such as acute ketoacidosis and liver dysfunction. Understanding the clinical comorbidities of ADP is crucial for avoiding missed diagnoses.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Murat Karaoglan, Gulper Nacarkahya
Summary: This study aimed to identify clinical and laboratory clues of Maturity-onset diabetes of the young (MODY) in children with atypical presentations of diabetes and found that measurable C-peptide in follow-up, family history of early-onset diabetes, and low daily dose of insulin are important predictors of MODY. The most common causative mutations were found in the GCK and HNF4A genes, with MODY2 showing a higher frequency of low DDI requirement and MODY1 showing higher beta-cell antibody negativity among children misdiagnosed with T1DM.
JOURNAL OF DIABETES
(2021)
Article
Endocrinology & Metabolism
Kevin Colclough, Sian Ellard, Andrew Hattersley, Kashyap Patel
Summary: Genetic testing for monogenic diabetes is primarily focused on mutations in maturity-onset diabetes of the young (MODY) genes, but this approach may miss mutations in patients without typical features. A study found that mutations in syndromic diabetes genes, particularly m.3243A>G and HNF1B, accounted for a significant portion of monogenic diabetes cases and often overlapped with non-syndromic monogenic diabetes.
Article
Medicine, General & Internal
Yun-Ni Lee, Mohammed S. B. Huda
Summary: Diabetes mellitus is a common condition that clinicians often encounter, with type 2 diabetes being the most common type. However, there are other important atypical forms like MODY and LADA that clinicians need to consider for accurate diagnosis and management.
Article
Endocrinology & Metabolism
Hui-Xuan Wu, Tian-Yao Chu, Junaid Iqbal, Hong-Li Jiang, Long Li, Yan-Xuan Wu, Hou-De Zhou
Summary: The study compared the incidence risk of cardio-cerebrovascular events in maturity onset diabetes of the young (MODY), type 1 diabetes, and type 2 diabetes. The results showed that the risk of cardio-cerebrovascular events in MODY is between that of type 1 diabetes and type 2 diabetes.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Environmental Sciences
Marco Tarasco, Paulo J. Gavaia, Anabela Bensimon-Brito, Fabrice P. Cordelieres, Tamara Santos, Gil Martins, Daniela T. de Castro, Nadia Silva, Elsa Cabrita, Maria J. Bebianno, Didier Y. R. Stainier, M. Leonor Cancela, Vincent Laize
Summary: The presence of microplastics in the aquatic ecosystem poses a major problem for the environment and human health. The capacity of organic pollutants to adsorb onto microplastic particles raises concerns, as it provides a new route for toxic compounds to enter the food web. This study provides new insights into the biological effects of pristine and/or contaminated microplastics on zebrafish.
Article
Cardiac & Cardiovascular Systems
Hadil El-Sammak, Bingyuan Yang, Stefan Guenther, Wenbiao Chen, Ruben Marin-Juez, Didier Y. R. Stainier
Summary: This study investigated the mechanisms of coronary revascularization during zebrafish cardiac regeneration. The results showed that Vegfc signaling is crucial for the proliferation of coronary endothelial cells and cardiomyocytes dedifferentiation and proliferation. Additionally, Emilin2a and Cxcl8a-Cxcr1 signaling pathways are also involved in coronary revascularization during cardiac regeneration.
CIRCULATION RESEARCH
(2022)
Article
Developmental Biology
Baptiste Coxam, Russell T. Collins, Melina Hussmann, Yvonne Huisman, Katja Meier, Simone Jung, Eireen Bartels-Klein, Anna Szymborska, Lise Finotto, Christian S. M. Helker, Didier Y. R. Stainier, Stefan Schulte-Merker, Holger Gerhardt
Summary: This study identifies blood flow and the extracellular protein Svep1 as co-modulators of blood vessel anastomosis in zebrafish embryos. Loss of Svep1 and reduction of blood flow both contribute to defective vessel anastomosis. The study also suggests that the Vegfa/Vegfr signaling pathway plays a role in the formation and lumenisation of blood vessels.
Article
Cell Biology
Michelle America, Naguissa Bostaille, Marie Eubelen, Maud Martin, Didier Y. R. Stainier, Benoit Vanhollebeke
Summary: This study reveals the molecular mechanisms underlying the interactions between Gpr124 and Frizzled in zebrafish and mammals, and provides insights into the evolution of Gpr124/Reck function in vertebrates.
Article
Biology
Yu Hsuan Carol Yang, Linford J. B. Briant, Christopher A. Raab, Sri Teja Mullapudi, Hans-Martin Maischein, Koichi Kawakami, Didier Y. R. Stainier
Summary: This study established an in vivo imaging model to investigate the modulation of pancreatic endocrine cell activity by autonomic innervation. The results demonstrate the crucial role of innervation in maintaining cellular connectivity and function in pancreatic islets.
Article
Biology
Jialing Qi, Annegret Rittershaus, Rashmi Priya, Shivani Mansingh, Didier Y. R. Stainier, Christian S. M. Helker, Victoria L. Bautch
Summary: This study reveals that endocardial cells interact with cardiomyocytes through dynamic membrane protrusions, which is essential for trabeculation. Loss of Apelin signaling, a peptide derived from cardiomyocytes, or its receptor in endocardial cells leads to reduced endocardial sprouting and hypotrabeculation.
Article
Genetics & Heredity
Bo Hu, Sara Lelek, Bastiaan Spanjaard, Hadil El-Sammak, Mariana Guedes Simoes, Janita Mintcheva, Hananeh Aliee, Ronny Schaefer, Alexander M. Meyer, Fabian Theis, Didier Y. R. Stainier, Daniela Panakova, Jan Philipp Junker
Summary: This study identifies specialized activated fibroblast cell states in the regenerating zebrafish heart using single-cell transcriptomics and spatiotemporal analysis, and reveals the origin of these cell states and the regulatory mechanism of endocardial fibroblast response.
Article
Multidisciplinary Sciences
Hyun-Taek Kim, Paolo Panza, Khrievono Kikhi, Yuko Nakamichi, Ann Atzberger, Stefan Guenther, Clemens Ruppert, Andreas Guenther, Didier Y. R. Stainier
Summary: This study reveals that WNT/RYK signaling plays a regulatory role in lung diseases and highlights the anti-inflammatory modulation of RYK signaling in lung development and homeostasis. These findings provide an animal model for further investigation of the etiology and therapeutic approaches to inflammatory lung diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Giulia L. M. Boezio, Shengnan Zhao, Josephine Gollin, Rashmi Priya, Shivani Mansingh, Stefan Guenther, Nana Fukuda, Felix Gunawan, Didier Y. R. Stainier
Summary: The epicardium, the outermost layer of the heart, plays an important role in regulating cardiac regeneration. This study investigated the interaction between the epicardium and myocardium during development by creating three models of epicardial impairment in zebrafish. The results showed that the epicardium is required for cardiomyocyte growth during early cardiac morphogenesis and identified FGF and VEGF signaling pathways as important regulators of ventricular growth.
DISEASE MODELS & MECHANISMS
(2023)
Article
Multidisciplinary Sciences
Kenny Mattonet, Frederike W. Riemslagh, Stefan Guenther, Karin D. Prummel, Gokul Kesavan, Stefan Hans, Ingo Ebersberger, Michael Brand, Alexa Burger, Sven Reischauer, Christian Mosimann, Didier Y. R. Stainier
Summary: This study reveals that Npas4l/Tal1/Lmo2 play a role in the fate decision between the endothelial and pronephron lineages. Npas4l induces the expression of the transcription factor genes etsrp, tall, and Imo2, which are crucial for endothelial specification.
Article
Multidisciplinary Sciences
Thomas Juan, Agatha Ribeiro da Silva, Barbara Cardoso, SoEun Lim, Violette Charteau, Didier Y. R. Stainier
Summary: Cardiac valves play a vital role in ensuring unidirectional blood flow through the heart. Researchers have identified several mechanosensory genes as key regulators of valve development, expanding our understanding of this process.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Melina Hussmann, Dorte Schulte, Sarah Weischer, Claudia Carlantoni, Hiroyuki Nakajima, Naoki Mochizuki, Didier Y. R. Stainier, Thomas Zobel, Manuel Koch, Stefan Schulte-Merker, Victoria L. Bautch
Summary: This study reveals the critical roles of Svep1 and Tie1 in the development of specific subpopulations of the zebrafish facial lymphatic network. It also shows that this aspect of the network is formed independently of Vegfc signaling. The findings demonstrate the importance of Tie1 signaling in lymphangiogenesis and blood vessel development in zebrafish.
Article
Genetics & Heredity
Jordan M. Welker, Vahan Serobyan, Elhamalsadat Zaker Esfahani, Didier Y. R. Stainier
Summary: Transcriptional adaptation (TA) is a mechanism that modulates gene expression in response to mutations in mRNA. Researchers found a 25-base pair element in the regulatory region of the adapting gene that showed similarity to a sequence in the mutant mRNA. This element can induce ectopic expression of a fluorescent reporter gene, indicating its importance in TA.
Article
Cell Biology
Hitoshi Watanabe, Wen Du, Jinsook Son, Lina Sui, Shun-ichiro Asahara, Irwin J. Kurland, Taiyi Kuo, Takumi Kitamoto, Yasutaka Miyachi, Rafael de Cabo, Domenico Accili
Summary: Sulfonylureas are effective and affordable antidiabetic drugs, but chronic use leads to secondary failure. Cytochrome b5 reductase 3 (Cyb5r3) down-regulation is identified as a mechanism of secondary SU failure and can be successfully reversed. Cyb5r3 activators can rescue secondary SU failure and potentially rehabilitate SU use in diabetes.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Medicine, Research & Experimental
Wen Du, Junqiang Wang, Taiyi Kuo, Liheng Wang, Wendy M. McKimpson, Jinsook Son, Hitoshi Watanabe, Takumi Kitamoto, Yunkyoung Lee, Remi J. Creusot, Lloyd E. Ratner, Kasi McCune, Ya-Wen Chen, Brendan H. Grubbs, Matthew E. Thornton, Jason Fan, Nishat Sultana, Bryan S. Diaz, Iyshwarya Balasubramanian, Nan Gao, Sandro Belvedere, Domenico Accili
Summary: The study demonstrates the potential of using the intestine as a source for cellular reprogramming to replace lost pancreatic beta cells in diabetes. By ablating FoxO1, the Paneth/goblet cell lineage can be converted into insulin-producing cells. Through a combination treatment targeting FOXO1, Notch, and TGF-beta, near normalization of glucose levels can be achieved in diabetic animals, accompanied by the generation of intestinal insulin-producing cells.
JOURNAL OF CLINICAL INVESTIGATION
(2022)