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Your search keyword '"Krumbach, O. H. F."' showing total 2 results
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2 results on '"Krumbach, O. H. F."'

1. A novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function

Author

Lam, M. T., Coppola, S., Krumbach, O. H. F., Prencipe, G., Insalaco, A., Cifaldi, C., Brigida, I., Zara, E., Scala, S., Di Cesare, S., Martinelli, S., Di Rocco, M., Pascarella, A., Niceta, M., Pantaleoni, F., Ciolfi, A., Netter, P., Carisey, A. F., Diehl, M., Akbarzadeh, M., Cont, F., Merli, P., Pastore, A., Mortera, S. L., Camerini, S., Farina, L., Buchholzer, M., Pannone, L., Cao, T. N., Coban-Akdemir, Z. H., Jhangiani, S. N., Muzny, D. M., Gibbs, R. A., Basso-Ricci, L., Chiriaco, M., Dvorsky, R., Putignani, L., Carsetti, R., Janning, P., Stray-Pedersen, A., Erichsen, H. C., Horne, A. C., Bryceson, Y. T., Torralba-Raga, L., Ramme, K., Rosti, V., Bracaglia, C., Messia, V., Palma, P., Finocchi, A., Locatelli, Franco, Chinn, I. K., Lupski, J. R., Mace, E. M., Cancrini, C., Aiuti, A., Ahmadian, M. R., Orange, J. S., De Benedetti, F., Tartaglia, M., Locatelli F. (ORCID:0000-0002-7976-3654), Lam, M. T., Coppola, S., Krumbach, O. H. F., Prencipe, G., Insalaco, A., Cifaldi, C., Brigida, I., Zara, E., Scala, S., Di Cesare, S., Martinelli, S., Di Rocco, M., Pascarella, A., Niceta, M., Pantaleoni, F., Ciolfi, A., Netter, P., Carisey, A. F., Diehl, M., Akbarzadeh, M., Cont, F., Merli, P., Pastore, A., Mortera, S. L., Camerini, S., Farina, L., Buchholzer, M., Pannone, L., Cao, T. N., Coban-Akdemir, Z. H., Jhangiani, S. N., Muzny, D. M., Gibbs, R. A., Basso-Ricci, L., Chiriaco, M., Dvorsky, R., Putignani, L., Carsetti, R., Janning, P., Stray-Pedersen, A., Erichsen, H. C., Horne, A. C., Bryceson, Y. T., Torralba-Raga, L., Ramme, K., Rosti, V., Bracaglia, C., Messia, V., Palma, P., Finocchi, A., Locatelli, Franco, Chinn, I. K., Lupski, J. R., Mace, E. M., Cancrini, C., Aiuti, A., Ahmadian, M. R., Orange, J. S., De Benedetti, F., Tartaglia, M., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated immune cells and is associated with a variable clinical spectrum having overlap with more common pathophysiologies. HLH is difficult to diagnose and can be part of inflammatory syndromes. Here, we identify a novel hematological/autoinflammatory condition (NOCARH syndrome) in four unrelated patients with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH. Patients shared the same de novo CDC42 mutation (Chr1:22417990C>T, p.R186C) and altered hematopoietic compartment, immune dysregulation, and inflammation. CDC42 mutations had been associated with syndromic neurodevelopmental disorders. In vitro and in vivo assays documented unique effects of p.R186C on CDC42 localization and function, correlating with the distinctiveness of the trait. Emapalumab was critical to the survival of one patient, who underwent successful bone marrow transplantation. Early recognition of the disorder and establishment of treatment followed by bone marrow transplant are important to survival.

Published
2019

2. A novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function

Author

Immacolata Brigida, Lamberto Torralba-Raga, Radovan Dvorsky, Silvia Di Cesare, Andrea Finocchi, AnnaCarin Horne, Ivan K. Chinn, Serena Scala, Simone Martinelli, Antonia Pascarella, Asbjørg Stray-Pedersen, Erika Zara, Marco Tartaglia, Emily M. Mace, Franco Locatelli, Luca Pannone, Stefano Levi Mortera, Claudia Bracaglia, Giusi Prencipe, Mohammad Akbarzadeh, Paolo Palma, Petra Janning, Anna Pastore, Rita Carsetti, Mohammad Reza Ahmadian, Fabrizio De Benedetti, Michael R. Diehl, Petra Netter, Shalini N. Jhangiani, Richard A. Gibbs, Caterina Cancrini, Tram N. Cao, James R. Lupski, Alexandre F. Carisey, Vittorio Rosti, Pietro Merli, Alessandro Aiuti, Zeynep H. Coban-Akdemir, Donna M. Muzny, Yenan T. Bryceson, Francesca Pantaleoni, Martina Di Rocco, Serena Camerini, Marcello Niceta, Virginia Messia, Cristina Cifaldi, Marcel Buchholzer, Andrea Ciolfi, Michael T. Lam, Hans Christian Erichsen, Antonella Insalaco, Kim Ramme, Oliver H.F. Krumbach, Francesca Conti, Luca Basso-Ricci, Simona Coppola, Jordan S. Orange, Maria Chiriaco, Lorenza Putignani, Luciapia Farina, Lam, M. T., Coppola, S., Krumbach, O. H. F., Prencipe, G., Insalaco, A., Cifaldi, C., Brigida, I., Zara, E., Scala, S., Di Cesare, S., Martinelli, S., Di Rocco, M., Pascarella, A., Niceta, M., Pantaleoni, F., Ciolfi, A., Netter, P., Carisey, A. F., Diehl, M., Akbarzadeh, M., Conti, F., Merli, P., Pastore, A., Levi Mortera, S., Camerini, S., Farina, L., Buchholzer, M., Pannone, L., Cao, T. N., Coban-Akdemir, Z. H., Jhangiani, S. N., Muzny, D. M., Gibbs, R. A., Basso-Ricci, L., Chiriaco, M., Dvorsky, R., Putignani, L., Carsetti, R., Janning, P., Stray-Pedersen, A., Erichsen, H. C., Horne, A., Bryceson, Y. T., Torralba-Raga, L., Ramme, K., Rosti, V., Bracaglia, C., Messia, V., Palma, P., Finocchi, A., Locatelli, F., Chinn, I. K., Lupski, J. R., Mace, E. M., Cancrini, C., Aiuti, A., Ahmadian, M. R., Orange, J. S., De Benedetti, F., and Tartaglia, M.

Subjects
Male, Models, Molecular, 0301 basic medicine, Molecular Conformation, medicine.disease_cause, Mice, 0302 clinical medicine, Immunology and Allergy, Child, cdc42 GTP-Binding Protein, Research Articles, Mutation, Rash, Phenotype, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Cdc42 GTP-Binding Protein, 030220 oncology & carcinogenesis, Female, Disease Susceptibility, biological phenomena, cell phenomena, and immunity, medicine.symptom, Protein Binding, HLH, Genotype, Immunology, Inflammation, macromolecular substances, Lymphohistiocytosis, Hemophagocytic, Article, 03 medical and health sciences, Immune system, Cell Line, Tumor, medicine, Animals, Humans, Alleles, Genetic Association Studies, Cytopenia, Hemophagocytic lymphohistiocytosis, Binding Sites, business.industry, Infant, Immune dysregulation, CDC42, dyshematopoiesis, inflammation, RHO-GTPase, medicine.disease, 030104 developmental biology, Amino Acid Substitution, business
Abstract

Lam et al. characterize a novel hematological/autoinflammatory disorder due to a de novo recurrent missense mutation of CDC42. The authors use in silico, in vitro, and in vivo analyses to correlate the molecular mechanisms altering CDC42 function to the observed phenotype., Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated immune cells and is associated with a variable clinical spectrum having overlap with more common pathophysiologies. HLH is difficult to diagnose and can be part of inflammatory syndromes. Here, we identify a novel hematological/autoinflammatory condition (NOCARH syndrome) in four unrelated patients with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH. Patients shared the same de novo CDC42 mutation (Chr1:22417990C>T, p.R186C) and altered hematopoietic compartment, immune dysregulation, and inflammation. CDC42 mutations had been associated with syndromic neurodevelopmental disorders. In vitro and in vivo assays documented unique effects of p.R186C on CDC42 localization and function, correlating with the distinctiveness of the trait. Emapalumab was critical to the survival of one patient, who underwent successful bone marrow transplantation. Early recognition of the disorder and establishment of treatment followed by bone marrow transplant are important to survival., Graphical Abstract

Published
2019

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