Article
Biochemistry & Molecular Biology
Tony Yammine, Raffi Aprahamian, Mirna Souaid, Nabiha Salem, Johnny Awwad, Chantal Farra
Summary: We report a Lebanese family with three patients diagnosed with congenital insensitivity to pain (CIP), who were found to have a novel pathogenic variant in the SCN9A gene through genetic investigation. In addition to the lack of pain perception, these patients also exhibited urinary incontinence, normal olfactory function, and osteoporosis and osteoarthritis, which is a previously unreported combination of features.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Neurosciences
Donald Iain MacDonald, Shafaq Sikandar, Jan Weiss, Martina Pyrski, Ana P. Luiz, Queensta Millet, Edward C. Emery, Flavia Mancini, Gian D. Iannetti, Sascha R. A. Alles, Manuel Arcangeletti, Jing Zhao, James J. Cox, Robert M. Brownstone, Frank Zufall, John N. Wood
Summary: Deletion of SCN9A encoding Na(V)1.7 in humans leads to pain insensitivity and anosmia. Knockout mice show normal nociceptor activity, but synaptic transmission from nociceptor terminals in the spinal cord is reduced by an opioid-dependent mechanism, reversing analgesia. This mechanism is also responsible for anosmia.
Review
Pharmacology & Pharmacy
David A. Eagles, Chun Yuen Chow, Glenn F. King
Summary: This review examines the role of Na(V)1.7 channels in nociception, their history as a therapeutic target, and the challenges in developing potent inhibitors. Despite significant progress in drug development, effective analgesia remains elusive in clinical trials.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Neurosciences
Xiao-hui Xie, Jian-guang Tang, Zhong-hua Liu, Shui-jiao Peng, Zhuang-zhuang Yuan, Heng Gu, Yi-qiao Hu, Zhi-ping Tan
Summary: Charcot neuroarthropathy associated with CIP has a wider spectrum than previously recognized, and the novel SCN9A mutation identified in this study contributes to understanding critical amino acids for maintaining Nav1.7 function, which is valuable for the development of Nav1.7-targeted analgesics.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Susie Barbeau, Fannie Semprez, Alexandre Dobbertin, Laurine Merriadec, Florine Roussange, Bruno Eymard, Damien Sternberg, Emmanuel Fournier, Hanice Karasoy, Cecile Martinat, Claire Legay
Summary: Congenital Myasthenic Syndromes (CMSs) are rare inherited diseases characterized by muscle weakness. In this study, a patient with a COLQ variant was analyzed, and it was found that the variant leads to decreased signaling and immature acetylcholine receptors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Chiho Sugisawa, Makoto Ono, Kenichi Kashimada, Tomonobu Hasegawa, Satoshi Narumi
Summary: A frameshift TSHR variant located in the intracytoplasmic C-tail region was identified and characterized in this study, affecting protein stability. The variant Val711Phefs*18-TSHR was found to have reduced protein expression and loss of function, while the similar Val711*-TSHR function remained intact. This study also demonstrated the impact of hydrophobicity in the C-terminal region on TSHR stability.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Endocrinology & Metabolism
Anojian Koneshamoorthy, Dilan Seniveratne-Epa, Genevieve Calder, Matthew Sawyer, Thomas W. H. Kay, Stephen Farrell, Thomas Loudovaris, Lina Mariana, Davis McCarthy, Ruqian Lyu, Xin Liu, Peter Thorn, Jason Tong, Lit Kim Chin, Margaret Zacharin, Alison Trainer, Shelby Taylor, Richard J. MacIsaac, Nirupa Sachithanandan, Helen E. Thomas, Balasubramanian Krishnamurthy
Summary: We present a case of an obese 22-year-old man with activating GCK variant who had neonatal hypoglycemia, re-emerging with hypoglycemia later in life. Genetic testing yielded a novel GCK missense class 3 variant that was subsequently found in his mother, sister and nephew and reclassified as a class 4 likely pathogenic variant. This case highlights the variable phenotype of GCK mutations.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Genetics & Heredity
Baker Elsana, Ahed Imtirat, Ronit Yagev, Libe Gradstein, Pierre Majdalani, Oren Iny, Ruti Parvari, Erez Tsumi
Summary: Congenital insensitivity to pain is a group of rare genetic disorders characterized by the absence of sensation to nociceptive pain. This study analyzed six patients with different gene variants and identified differences in ocular manifestations between the PRDM12 and SCN9A variants, with PRDM12 variant patients showing more severe ocular surface disease.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Anesthesiology
Margherita Marchi, Ilaria D'Amato, Mirna Andelic, Daniele Cartelli, Erika Salvi, Raffaella Lombardi, Evren Gumus, Giuseppe Lauria
Summary: Mutations in SCN9A gene can lead to a wide range of clinical outcomes related to pain sensitivity. This study describes a patient born from consanguineous parents who exhibited pain insensitivity, diminished temperature sensation, foot burns, and loss of nociceptive nerve fibers. Through genetic sequencing and functional studies, a novel mutation in SCN9A gene causing pain insensitivity was identified.
Review
Pharmacology & Pharmacy
Wayra Brackx, Rita de Cassia Collaco, Margaux Theys, Jolien Vander Cruyssen, Frank Bosmans
Summary: Voltage-activated Na+ (NaV) channels are important for electrical signaling in the human body and are targeted by therapeutic drugs and toxins. Some NaV channel subtypes play roles in pain and other sensory processes, while the physiological role of NaV1.9 is not well understood. Mutations in NaV1.9 can lead to sensory-related diseases. This review explores the mechanisms of NaV1.9 in pain and discusses the need for comprehensive understanding of NaV1.9-specific pharmacology.
PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Orthopedics
Yuhao Jiao, Ye Tian, Siyi Cai
Summary: This article discusses a rare case of congenital insensitivity to pain with anhidrosis (CIPA) with Charcot arthropathy. The author summarizes the choices of surgical strategies and alerts clinicians to post-surgery complications based on a 10-year follow-up. The possible underlying reasons for recurrent Charcot arthropathies and strategies for peri-operative management in such cases are also discussed.
ORTHOPAEDIC SURGERY
(2023)
Article
Neurosciences
Mi Zhang, Yishun Hong, Wenyao Wu, Ningbo Li, Baowen Liu, Jiaoli Sun, Xueqin Cao, Ting Ye, Ling Zhou, Cunming Liu, Chun Yang, Xianwei Zhang
Summary: The gut microbiota of CIPA patients plays a key role in behaviors. Fecal microbiota transplantation has significant effects on the behavior of experimental mice, indicating potential therapeutic strategies for alleviating CIPA symptoms.
PSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
Qi Tian, Li Shu, Pu Zhang, Ting Zeng, Yang Cao, Hui Xi, Ying Peng, Yaqin Wang, Xiao Mao, Hua Wang
Summary: MN1 C-terminal truncation (MCTT) syndrome, caused by variants in the C-terminal region of MN1 gene, presents with a wide range of clinical features. Our study reported a patient with mild developmental delay and normal brain MRI due to a de novo MN1 variant, expanding the clinical and genetic spectrum of MCTT.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Endocrinology & Metabolism
Zhiyuan Zhao, Yinjie Gao, Lin Lu, Anli Tong, Shi Chen, Wei Zhang, Xiaoxia Zhang, Bang Sun, Xueyan Wu, Jiangfeng Mao, Xi Wang, Min Nie
Summary: This study analyzed the relationship between genotype and phenotype in 21-Hydroxylase deficiency patients harboring P31L variant and the underlying mechanism. The findings suggest that the high incidence (57.4%) of simple virilizing form in these patients is partially due to both the promoter variants and P31L aligning in cis on one allele.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Medicine, General & Internal
Rong Zhu, Yuxiang Zhu, Mingpeng Xu, Zhensheng Gu
Summary: We present a case of CIPA with a new NTRK1 gene mutation, in which the patient experienced recurrent corneal ulcer. Genetic sequencing revealed compound-heterozygous mutations in NTRK1 gene. After medication, the corneal ulcer of the patient healed. This study expands the spectrum of NTRK1 gene mutation associated with CIPA and provides a feasible approach for clinicians to treat patients with CIPA-related keratopathy.
FRONTIERS IN MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Lukas Soellner, Florian Kraft, Sabrina Sauer, Matthias Begemann, Ingo Kurth, Miriam Elbracht, Thomas Eggermann
EUROPEAN JOURNAL OF HUMAN GENETICS
(2019)
Article
Biochemistry & Molecular Biology
Laura Behrendt, Ingo Kurth, Christoph Kaether
CELLULAR AND MOLECULAR LIFE SCIENCES
(2019)
Article
Biochemistry & Molecular Biology
Michiel Krols, Bob Asselbergh, Riet De Rycke, Vicky De Winter, Alexandre Seyer, Franz-Josef Mueller, Ingo Kurth, Geert Bultynck, Vincent Timmerman, Sophie Janssens
HUMAN MOLECULAR GENETICS
(2019)
Article
Genetics & Heredity
Paola Fortugno, Francesco Angelucci, Gianluca Cestra, Letizia Camerota, Angelo Salvatore Ferraro, Sonia Cordisco, Luigi Uccioli, Daniele Castiglia, Barbara De Angelis, Ingo Kurth, Uwe Kornak, Francesco Brancati
Article
Medicine, General & Internal
Maike F. Dohrn, Angelika Lampert, Nurcan Ueceyler, Ingo Kurth
Article
Medicine, Research & Experimental
Gergely Karsai, Florian Kraft, Natja Haag, G. Christoph Korenke, Benjamin Haenisch, Alaa Othman, Saranya Suriyanarayanan, Regula Steiner, Cordula Knopp, Michael Mull, Markus Bergmann, J. Michael Schroeder, Joachim Weis, Miriam Elbracht, Matthias Begemann, Thorsten Hornemann, Ingo Kurth
JOURNAL OF CLINICAL INVESTIGATION
(2019)
Article
Multidisciplinary Sciences
Christoph Ammer-Herrmenau, Upasana Kulkarni, Nico Andreas, Martin Ungelenk, Sarina Ravens, Christian Huebner, Angela Kather, Ingo Kurth, Michael Bauer, Thomas Kamradt
Article
Cell & Tissue Engineering
Thomas Klein, Katharina Klug, Lisa Henkel, Chee Keong Kwok, Frank Edenhofer, Eva Klopocki, Ingo Kurth, Nurcan Ueceyler
STEM CELL RESEARCH
(2019)
Article
Oncology
Florian Kraft, Katharina Wesseler, Matthias Begemann, Ingo Kurth, Miriam Elbracht, Thomas Eggermann
CLINICAL EPIGENETICS
(2019)
Article
Genetics & Heredity
Robert Meyer, Matthias Begemann, Stephanie Demuth, Florian Kraft, Daniela Dey, Herdit Schueler, Sabine Busse, Martin Haeusler, Klaus Zerres, Ingo Kurth, Thomas Eggermann, Miriam Elbracht
Review
Biochemistry & Molecular Biology
Florian Kraft, Ingo Kurth
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2020)
Article
Hematology
Miriam Elbracht, Robert Meyer, Kim Kricheldorf, Deniz Gezer, Thomas Eggermann, Beate Betz, Ingo Kurth, Lino L. Teichmann, Tim H. Bruemmendorf, Ulrich Germing, Susanne Isfort, Steffen Koschmieder
Summary: The study identified germline mutations in MPNs patients, suggesting a higher risk of leukemia; the discovery of hereditary tumor predisposition is crucial for therapeutic options and preventive care for individuals with MPNs in their families.
Article
Medicine, General & Internal
Martin Kirschner, Inga Rebecca Heinen, Steffen Koschmieder, Licinio Manco, Celeste Bento, Thomas Eggermann, Ingo Kurth, Edgar Jost, Tim H. Bruemmendorf, Roland Fuchs
Summary: A new mutation in a Turkish family is described, confirming the association between homozygous mutational state and clinical manifestation of P5'N-1 deficiency.
CLINICAL CASE REPORTS
(2022)
Article
Genetics & Heredity
Yaoxian Xu, Christoph Kuppe, Javier Perales-Paton, Sikander Hayat, Jennifer Kranz, Ali T. Abdallah, James Nagai, Zhijian Li, Fabian Peisker, Turgay Saritas, Maurice Halder, Sylvia Menzel, Konrad Hoeft, Annegien Kenter, Hyojin Kim, Claudia R. C. van Roeyen, Michael Lehrke, Julia Moellmann, Thimoteus Speer, Eva M. Buhl, Remco Hoogenboezem, Peter Boor, Jitske Jansen, Cordula Knopp, Ingo Kurth, Bart Smeets, Eric Bindels, Marlies E. J. Reinders, Carla Baan, Joost Gribnau, Ewout J. Hoorn, Joachim Steffens, Tobias B. Huber, Ivan Costa, Jurgen Floege, Rebekka K. Schneider, Julio Saez-Rodriguez, Benjamin S. Freedman, Rafael Kramann
Summary: Adult kidney organoids, known as tubuloids, are derived from a distinct CD24(+) epithelial subpopulation and can be used to model autosomal dominant polycystic kidney disease (ADPKD) and study drug response. The study found similarities in gene expression between gene-edited tubuloids and ADPKD patients' tissue, demonstrating the potential of tubuloids in ADPKD disease modeling. Additionally, the approved drug for ADPKD, tolvaptan, was found to have a significant effect on cyst size in tubuloids but not in pluripotent stem cell-derived models.
Article
Infectious Diseases
Torsten Houwaart, Samir Belhaj, Emran Tawalbeh, Dirk Nagels, Yara Froehlich, Patrick Finzer, Pilar Ciruela, Aurora Sabria, Merce Herrero, Cristina Andres, Andres Anton, Assia Benmoumene, Dounia Asskali, Hussein Haidar, Janina von Dahlen, Jessica Nicolai, Mygg Stiller, Jacqueline Blum, Christian Lange, Carla Adelmann, Britta Schroer, Ute Osmers, Christiane Grice, Phillipp P. Kirfel, Hassan Jomaa, Daniel Strelow, Lisanna Huelse, Moritz Pigulla, Pascal Kreuzer, Alona Tyshaieva, Jonas Weber, Tobias Wienemann, Malte Kohns Vasconcelos, Katrin Hoffmann, Nadine Luebke, Sandra Hauka, Marcel Andree, Claus Jurgen Scholz, Nathalie Jazmati, Klaus Goebels, Rainer Zotz, Klaus Pfeffer, Jorg Timm, Lutz Ehlkes, Andreas Walker, Alexander T. Dilthey
Summary: This study demonstrates the successful application of an integrated genomic surveillance system in tracing the transmission chains of SARS-CoV-2 and investigating travel-associated infection clusters. The findings show the presence of two genetically defined clusters of SARS-CoV-2 isolates in Dusseldorf, with one cluster linked to nightlife venues and a returning traveler, and the other cluster representing multiple independent introductions followed by community transmission.
