Article
Genetics & Heredity
Alexandra Kehl, Anita Haug Haaland, Ines Langbein-Detsch, Elisabeth Mueller
Summary: The study identified a SINE insertion in exon 14 of the F8 gene as the genetic cause of Hemophilia A in a family of Rhodesian Ridgebacks. This genetic variant was confirmed through Sanger sequencing and its perfect correlation with clinical signs in the family tree was established. Additionally, clinically unaffected female carriers were identified and recommended to be excluded from breeding to prevent the production of clinically affected male offspring and more subclinical female carriers.
Article
Hematology
Roeland Huijgen, Dirk J. Blom, Merel L. Hartgers, Kevin Chemello, Asier Benito-Vicente, Kepa B. Uribe, Zorena Behardien, Dee M. Blackhurst, Brigitte C. Brice, Joep C. Defesche, Annemiek G. de Jong, Rosemary J. Jooste, Bharati D. Ratanjee, Gabriele A. E. Solomon, Karen H. Wolmarans, G. Kees Hovingh, Cesar Martin, Gilles Lambert, A. David Marais
Summary: Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein-cholesterol and increased cardiovascular risk. In this study, we evaluated the impact of novel PCSK9 variants in FH patients through genetic cascade screening and functionality assays. Approximately 1.14% of FH cases were clearly attributed to pathogenic variants in PCSK9, with the G516V variant's pathogenicity firmly established.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Genetics & Heredity
Siren Berland, Bjorn Ivar Haukanes, Petur Benedikt Juliusson, Gunnar Houge
Summary: This study reports on a boy with a mixture of Beckwith-Wiedemann syndrome (BWS) and IMAGe syndrome, along with additional features of developmental delay and microcephaly. The researchers identified a variant in the CDKN1C gene that resulted in the production of three different RNA products, explaining the co-occurring features of both syndromes.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Genetics & Heredity
Alka Malhotra, Alban Ziegler, Li Shu, Renee Perrier, Louise Amlie-Wolf, Elizabeth Wohler, Nara Lygia de Macena Sobreira, Estelle Colin, Adeline Vanderver, Omar Sherbini, Katrien Stouffs, Emmanuel Scalais, Alessandro Serretti, Magalie Barth, Benjamin Navet, Paul Rollier, Hui Xi, Hua Wang, Hainan Zhang, Denise L. Perry, Alessandra Ferrarini, Roberto Colombo, Alexander Pepler, Adele Schneider, Kiyotaka Tomiwa, Nobuhiko Okamoto, Naomichi Matsumoto, Noriko Miyake, Ryan Taft, Xiao Mao, Dominique Bonneau
Summary: Rare de novo variants in LMBRD2 were identified in 10 individuals with developmental delay, intellectual disability, thin corpus callosum, microcephaly and seizures. These findings suggest that these variants may cause a previously unrecognized early-onset neurodevelopmental disorder.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Clinical Neurology
Andreas Brunklaus, Tobias Bruenger, Tony Feng, Carmen Fons, Anni Lehikoinen, Eleni Panagiotakaki, Mihaela-Adela Vintan, Joseph Symonds, James Andrew, Alexis Arzimanoglou, Sarah Delima, Julie Gallois, Donncha Hanrahan, Gaetan Lesca, Stewart MacLeod, Dragan Marjanovic, Amy McTague, Noemi Nunez-Enamorado, Eduardo Perez-Palma, M. Scott Perry, Karen Pysden, Sophie J. Russ-Hall, Ingrid E. Scheffer, Krystal Sully, Steffen Syrbe, Ulvi Vaher, Murugan Velayutham, Julie Vogt, Shelly Weiss, Elaine Wirrell, Sameer M. Zuberi, Dennis Lal, Rikke S. Moller, Massimo Mantegazza, Sandrine Cestele
Summary: This study describes different phenotypes of SCN1A-related epilepsy, some of which are associated with febrile seizures and familial hemiplegic migraine. The research found that these phenotypes are caused by SCN1A variants, and by conducting clinical, genetic, and functional evaluations of the affected individuals, it reveals the potential efficacy of sodium channel blockers in treating this disease.
Article
Biochemistry & Molecular Biology
Tong Lu, Xiaojing Sun, Brian M. Necela, Hon-Chi Lee, Nadine Norton
Summary: The N338S mutant of the TRPC6 gene is a gain-of-function mutation that leads to increased Ca2+ influx and [Ca2+](i) in cardiomyocytes, potentially contributing to DOX-induced cardiotoxicity.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Hematology
Frederic Adam, Alexandre Kauskot, Lamia Lamrani, Jean Solarz, Christelle Soukaseum, Christelle Reperant, Cecile Denis, Hana Raslova, Jean-Philippe Rosa, Marijke Bryckaert
Summary: This study investigates the thrombotic potential of a male patient with a FLNa mutation in an in vivo model. They establish a mutant FlnA knock-in mouse model which phenocopies the patient's platelets showing increased platelet functions in vitro. However, in vivo, the mutant FlnA mice exhibit thrombus instability evidenced by increased re-bleeding and arteriolar embolies.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Genetics & Heredity
Masashi Nishikawa, Marcello Scala, Muhammad Umair, Hidenori Ito, Ahmed Waqas, Pasquale Striano, Federico Zara, Gregory Costain, Valeria Capra, Koh-ichi Nagata
Summary: In this study, a novel RAC3 variant (p.F28S) was identified to play a critical role in brain development, leading to morphological and functional defects in cortical neurons, likely due to hyperactivation of PAK1.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Immunology
Basak Kayaoglu, Nurhan Kasap, Naz Surucu Yilmaz, Louis Marie Charbonnier, Busranur Geckin, Arzu Akcay, Sevgi Bilgic Eltan, Gulyuz Ozturk, Ahmet Ozen, Elif Karakoc-Aydiner, Talal A. Chatila, Mayda Gursel, Safa Baris
Summary: This study investigated the effect of ruxolitinib as a bridge therapy in managing infections and other disease manifestations in a patient with sporadic STAT1 T385M mutation. Ruxolitinib provided favorable responses in controlling candidiasis and autoimmune hemolytic anemia, improved dysregulation in STAT1 phosphorylation kinetics, and normalized T(H)17 deficiency after transplantation. Dysregulated gene expression related to immune pathways was partially improved with ruxolitinib treatment and completely normalized after transplantation, suggesting potential benefits in reducing the risk of adverse outcomes of HSCT.
JOURNAL OF CLINICAL IMMUNOLOGY
(2021)
Review
Physiology
Jianmin Cui
Summary: This article discusses the activation mechanisms of BK channels and their association with neurological disorders, highlighting the significance of these mechanisms in neurophysiology.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Allergy
Panfeng Tao, Xu Han, Qintao Wang, Shihao Wang, Jiahui Zhang, Lin Liu, Xiaorui Fan, Chenlu Liu, Meng Liu, Li Guo, Pui Y. Lee, Ivona Aksentijevich, Qing Zhou
Summary: This study highlights the critical role of PLCy1 in maintaining immune homeostasis and illustrates immune dysregulation as a consequence of PLCy1 activation. Additionally, we provide insight into therapeutic targeting of PLCy1.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Plant Sciences
Maiara Piovesana, Ana K. M. Wood, Daniel P. Smith, Michael J. Deery, Richard Bayliss, Esther Carrera, Nikolaus Wellner, Ondrej Kosik, Johnathan A. Napier, Smita Kurup, Michaela C. Matthes
Summary: The crk10-A397T mutant of Arabidopsis, characterized by the replacement of alanine 397 with threonine in the kinase domain of CRK10, exhibits a dwarf phenotype with collapsed xylem vessels in the root and hypocotyl. Transcriptomic analysis reveals constitutive upregulation of stress-responsive genes in the mutant, and a root-infection assay demonstrates enhanced resistance to the pathogen Fusarium oxysporum. The mutant is identified as a gain-of-function allele of CRK10 in Arabidopsis.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Letter
Genetics & Heredity
Raymond F. Sekula, Kathleen Deeley, Hayley Denwood, Alexandre R. Vieira
Summary: The Met136Val mutation in SCN8A was identified in a case of trigeminal neuralgia, but it was not found in any of the 123 individuals diagnosed with classic trigeminal neuralgia. This suggests that the Met136Val mutation is not a common cause of classical trigeminal neuralgia.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Bi-He Cai, Yun-Chien Hsu, Fang-Yu Yeh, Yu-Rou Lin, Rui-Yu Lu, Si-Jie Yu, Jei-Fu Shaw, Ming-Han Wu, Yi-Zhen Tsai, Ying-Chen Lin, Zhi-Yu Bai, Yu-Chen Shih, Yi-Chiang Hsu, Ruo-Yu Liao, Wei-Hsin Kuo, Chao-Tien Hsu, Ching-Feng Lien, Chia-Chi Chen
Summary: p53 family members p53, p63, and p73 have tumor suppressor function, but p53 has a high mutation rate in cancers causing loss of its function. This review discusses drug therapies for nonsense and missense mutations in p53, and proposes p63 and p73 activators as potential anti-cancer drugs to replace mutant p53. Strategies to improve the response of these activators, particularly for p53 gain-of-function mutants, are also discussed.
Article
Genetics & Heredity
Xihan Guo, Minyan Jiang, Xueqin Dai, Jie Shen, Xu Wang
Summary: Mutations in Presenilin-1 (PS1) are responsible for the majority of familial Alzheimer's disease (AD) cases. This study demonstrates that knocking down PS1 or inhibiting its gamma-secretase activity induces genome instability, which may contribute to the development of AD. The findings suggest a potential link between PS1 loss-of-function or gain-of-function mutations and familial AD through the impairment of genome stability.
Article
Cell Biology
Nicolas Houde, Laurent Beuret, Amelie Bonaud, Simon-Pierre Fortier-Beaulieu, Kim Truchon-Landry, Rifdat Aoidi, Emilie Pic, Nagham Alouche, Vincent Rondeau, Geraldine Schlecht-Louf, Karl Balabanian, Marion Espeli, Jean Charron
Summary: This study reveals the critical role of fine-tuning the ERK/MAPK pathway in immune cell activation and function. It also demonstrates that MEK1 and MEK2 isoforms play distinct roles in lymphocyte activation and disease development.
Article
Oncology
Louise Rethacker, Maxime Boy, Valeria Bisio, France Roussin, Jordan Denizeau, Anne Vincent-Salomon, Edith Borcoman, Christine Sedlik, Eliane Piaggio, Antoine Toubert, Nicolas Dulphy, Anne Caignard
Summary: Innate lymphoid cells (ILCs), including NK cells and ILC3, play important roles in tissue immune homeostasis and tumor surveillance. In human lymph nodes, NK cells and ILC3s are the prominent subpopulations. However, in tumor-draining lymph nodes and breast cancer tumors, NK cells are more abundant while proportions of ILC3 subsets are low. The local tumor microenvironment inhibits NK cell functions through downregulation of a specific receptor, but cytokine stimulation can restore their functionality.
Editorial Material
Medicine, Research & Experimental
Nicolas Houde, Marion Espeli, Jean Charron
M S-MEDECINE SCIENCES
(2022)
Article
Immunology
Amelie Bonaud, Melanie Khamyath, Marion Espeli
Summary: Plasma cells and their antibodies play a crucial role in protection against infection, but can also be involved in diseases such as autoimmune diseases and multiple myeloma. The differentiation and survival of plasma cells are regulated by transcriptional switches and morphological changes. Although some cellular and molecular mechanisms have been identified, the mechanisms by which plasma cells survive and secrete large quantities of antibodies for extended periods of time remain unclear. This review aims to discuss the current understanding of plasma cell cellular biology, the challenges faced by research in this field, and the potential opportunities for studying the fundamental mechanisms underlying plasma cell survival and function.
IMMUNOLOGY LETTERS
(2023)
Article
Medicine, Research & Experimental
Melanie Khamyath, Amelie Bonaud, Karl Balabanian, Marion Espeli
Summary: CXCR4 plays a crucial role in cell migration and the development of the immune system. It is involved in B lymphocyte biology from their differentiation to plasma cell formation. Mutations in CXCR4 can lead to a rare immunodeficiency called the WHIM Syndrome, affecting receptor desensitization and increasing response to its ligand CXCL12. This review emphasizes the regulatory role of CXCR4 desensitization in humoral immune responses, using the WHIM Syndrome as an example, and highlights the importance of fine-tuning CXCR4 signaling for long-term antibody-mediated protection.
M S-MEDECINE SCIENCES
(2023)
Article
Multidisciplinary Sciences
Amelie Bonaud, Laetitia Gargowitsch, Simon M. Gilbert, Elanchezhian Rajan, Pablo Canales-Herrerias, Daniel Stockholm, Nabila F. Rahman, Mark O. Collins, Hakan Taskiran, Danika L. Hill, Andres Alloatti, Nagham Alouche, Stephanie Balor, Vanessa Soldan, Daniel Gillet, Julien Barbier, Francoise Bachelerie, Kenneth G. C. Smith, Julia Jellusova, Pierre Bruhns, Sebastian Amigorena, Karl Balabanian, Michelle A. Linterman, Andrew A. Peden, Marion Espeli
Summary: We identified SNARE Sec22b as a critical regulator of plasma cell maintenance and function. In the absence of Sec22b, plasma cells were hardly detectable and serum antibody titers were dramatically reduced, leading to a failure in mounting a protective immune response. Mechanistically, Sec22b contributes to efficient antibody secretion and is involved in regulating plasma cell transcriptional identity, as well as the morphology of the endoplasmic reticulum and mitochondria.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Maxime Boy, Valeria Bisio, Lin-Pierre Zhao, Fabien Guidez, Berenice Schell, Emilie Lereclus, Guylaine Henry, Juliette Villemonteix, Fernando Rodrigues-Lima, Katia Gagne, Christelle Retiere, Lise Larcher, Rathana Kim, Emmanuelle Clappier, Marie Sebert, Arsene Mekinian, Olivier Fain, Anne Caignard, Marion Espeli, Karl Balabanian, Antoine Toubert, Pierre Fenaux, Lionel Ades, Nicolas Dulphy
Summary: NK cells in MDS patients with TET2 mutations exhibit phenotypic defects, including increased DNA methylation, reduced expression of KIR, perforin, and TNF-a. Inhibition of TET2 in NK cells from healthy donors decreases their cytotoxicity, indicating its critical role in NK cell function. Treatment with azacytidine enhances KIR and cytolytic protein expression, as well as IFN-gamma production in NK cells from patients.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Lin-Pierre Zhao, Marie Sebert, Arsene Mekinian, Olivier Fain, Marion Espeli, Karl Balabanian, Nicolas Dulphy, Lionel Ades, Pierre Fenaux
Article
Immunology
Alyssa Silva-Cayetano, Sigrid Fra-Bido, Philippe A. Robert, Silvia Innocentin, Alice R. Burton, Emily M. Watson, Jia Le Lee, Louise M. C. Webb, William S. Foster, Ross C. J. McKenzie, Alexandre Bignon, Ine Vanderleyden, Dominik Alterauge, Julia P. Lemos, Edward J. Carr, Danika L. Hill, Isabella Cinti, Karl Balabanian, Dirk Baumjohann, Marion Espeli, Michael Meyer-Hermann, Alice E. Denton, Michelle A. Linterman
Summary: Linterman and colleagues find that dysregulated CXCR4 expression in aged T-FH cells leads to their mislocation in germinal centers, impairing their ability to support B cell help and antibody production. The decline in the germinal center response with age results in poor vaccine-induced immunity in older individuals. However, this age-dependent defect can be reversed by providing T-FH cells that colocalize with follicular dendritic cells using CXCR5, highlighting the importance of T-FH cell localization in the antibody response and expansion of the FDC network.
Article
Multidisciplinary Sciences
Adrienne Anginot, Julie Nguyen, Zeina Abou Nader, Vincent Rondeau, Amelie Bonaud, Maria Kalogeraki, Antoine Boutin, Julia P. Lemos, Valeria Bisio, Joyce Koenen, Lea Hanna Doumit Sakr, Amandine Picart, Amelie Coudert, Sylvain Provot, Nicolas Dulphy, Michel Aurrand-Lions, Stephane J. C. Mancini, Gwendal Lazennec, David H. McDermott, Fabien Guidez, Claudine Blin-Wakkach, Philip M. Murphy, Martine Cohen-Solal, Marion Espeli, Matthieu Rouleau, Karl Balabanian
Summary: WHIM Syndrome is a rare immunodeficiency caused by mutations in CXCR4 gene. This study found that 25% of WHIM patients have decreased bone mineral density and bone defects leading to osteoporosis. The researchers also discovered that impaired CXCR4 signaling disrupts cell cycle progression and osteogenic commitment of skeletal stromal/stem cells, resulting in imbalanced bone tissue.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Amelie Bonaud, Pierre Larraufie, Melanie Khamyath, Ugo Szachnowski, Shaun M. Flint, Nadege Brunel-Meunier, Francois Delhommeau, Annie Munier, Tapio Loennberg, Claire Toffano-Nioche, Daniel Gautheret, Karl Balabanian, Marion Espeli
Summary: Using single cell RNAseq and in silico transinteractome analyses, the researchers identified Leptin receptor positive (LepR(+)) mesenchymal cells as the stromal cell subset most likely to interact with long-lived plasma cells (PCs) within the bone marrow. Furthermore, they found that PCs may use different sets of integrins and adhesion molecules to interact with these stromal cells based on their isotype. These findings provide new insights into the specific targeting of bone marrow PCs.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Vincent Jachiet, Laure Ricard, Pierre Hirsch, Florent Malard, Laurent Pascal, Odile Beyne-Rauzy, Pierre Peterlin, Alexandre Thibault Jacques Maria, Norbert Vey, Maud D'Aveni, Marie-Pierre Gourin, Sophie Dimicoli-Salazar, Anne Banos, Stefan Wickenhauser, Louis Terriou, Benoit De Renzis, Eric Durot, Shanti Natarajan-Ame, Anne Vekhoff, Laurent Voillat, Sophie Park, Julien Vinit, Celine Dieval, Azeddine Dellal, Vincent Grobost, Lise Willems, Julien Rossignol, Eric Solary, Olivier Kosmider, Nicolas Dulphy, Lin Pierre Zhao, Lionel Ades, Pierre Fenaux, Olivier Fain, Mohamad Mohty, Beatrice Gaugler, Arsene Mekinian
Summary: Background systemic inflammatory and autoimmune diseases (SIADs) occur in a significant proportion of myelodysplastic syndrome (MDS) patients. The recently identified VEXAS syndrome, associated with somatic mutations in UBA1, is characterized by severe inflammatory conditions and hematological abnormalities, including MDS. However, the mechanisms underlying the association between MDS and SIADs are largely unknown. This study aimed to evaluate myeloid immune cell subsets in MDS patients with and without SIAD and compare them to healthy controls.
CLINICAL AND EXPERIMENTAL MEDICINE
(2023)