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3. FDX2 and ISCU Gene Variations Lead to Rhabdomyolysis With Distinct Severity and Iron Regulation

Author

Montealegre, Sebastian, Lebigot, Elise, Debruge, Hugo, Romero, Norma, Héron, Bénédicte, Gaignard, Pauline, Legendre, Antoine, Imbard, Apolline, Gobin, Stéphanie, Lacène, Emmanuelle, Nusbaum, Patrick, Hubas, Arnaud, Desguerre, Isabelle, Servais, Aude, Laforêt, Pascal, van Endert, Peter, Authier, François Jérome, Gitiaux, Cyril, and de Lonlay, Pascale

Published
2022
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5. TUBG1 missense variants underlying cortical malformations disrupt neuronal locomotion and microtubule dynamics but not neurogenesis

Author

Ivanova, Ekaterina L., Gilet, Johan G., Sulimenko, Vadym, Duchon, Arnaud, Rudolf, Gabrielle, Runge, Karen, Collins, Stephan C., Asselin, Laure, Broix, Loic, Drouot, Nathalie, Tilly, Peggy, Nusbaum, Patrick, Vincent, Alexandre, Magnant, William, Skory, Valerie, Birling, Marie-Christine, Pavlovic, Guillaume, Godin, Juliette D., Yalcin, Binnaz, Hérault, Yann, Dráber, Pavel, Chelly, Jamel, and Hinckelmann, Maria-Victoria

Published
2019
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10. Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises and no primary energetic defect

Author

Bérat, Claire‐Marine, primary, Montealegre, Sebastian, additional, Wiedemann, Arnaud, additional, Nuzum, Malou Le Corronc, additional, Blondel, Amélie, additional, Debruge, Hugo, additional, Cano, Aline, additional, Chabrol, Brigitte, additional, Hoebeke, Célia, additional, Polak, Michel, additional, Stoupa, Athanasia, additional, Feillet, François, additional, Torre, Stéphanie, additional, Boddaert, Nathalie, additional, Bruel, Henri, additional, Barth, Magalie, additional, Damaj, Lena, additional, Abi‐Wardé, Marie‐Thérèse, additional, Afenjar, Alexandra, additional, Benoist, Jean‐François, additional, Madrange, Marine, additional, Caccavelli, Laure, additional, Renard, Perrine, additional, Hubas, Arnaud, additional, Nusbaum, Patrick, additional, Pontoizeau, Clément, additional, Gobin, Stéphanie, additional, Endert, Peter, additional, Ottolenghi, Chris, additional, Maltret, Alice, additional, and Lonlay, Pascale, additional

Published
2020
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16. Inhibition of IFNα secretion in cells from patients with juvenile dermatomyositis under TBK1 inhibitor treatment revealed by single-molecular assay technology

Author

Gitiaux, Cyril, primary, Bondet, Vincent, primary, Bekaddour, Nassima, primary, Nusbaum, Patrick, primary, Hubas, Arnaud, primary, Melki, Isabelle, primary, Bodemer, Christine, primary, Quartier, Pierre, primary, Desguerre, Isabelle, primary, Crow, Yanick J, primary, Herbeuval, Jean-Philippe, primary, Duffy, Darragh, primary, Bader Meunier, Brigitte , primary, and Rodero, Mathieu P, primary

Published
2020
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17. Inhibition of IFNα secretion in cells from patients with juvenile dermatomyositis under TBK1 inhibitor treatment revealed by single-molecular assay technology

Author

Gitiaux, Cyril, primary, Bondet, Vincent, primary, Bekaddour, Nassima, primary, Nusbaum, Patrick, primary, Hubas, Arnaud, primary, Melki, Isabelle, primary, Bodemer, Christine, primary, Quartier, Pierre, primary, Desguerre, Isabelle, primary, Crow, Yanick J, primary, Herbeuval, Jean-Philippe, primary, Duffy, Darragh, primary, Bader Meunier, Brigitte, primary, and Rodero, Mathieu P, primary

Published
2019
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19. Myogenic Progenitor Cells Exhibit Type I Interferon–Driven Proangiogenic Properties and Molecular Signature During Juvenile Dermatomyositis

Author

Gitiaux, Cyril, primary, Latroche, Claire, additional, Weiss‐Gayet, Michèle, additional, Rodero, Mathieu P., additional, Duffy, Darragh, additional, Bader‐Meunier, Brigitte, additional, Glorion, Christophe, additional, Nusbaum, Patrick, additional, Bodemer, Christine, additional, Mouchiroud, Guy, additional, Chelly, Jamel, additional, Germain, Stéphane, additional, Desguerre, Isabelle, additional, and Chazaud, Bénédicte, additional

Published
2017
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20. Additional file 7: Figure S3. of Dp412e: a novel human embryonic dystrophin isoform induced by BMP4 in early differentiated cells

Author

Massouridès, Emmanuelle, Polentes, Jérôme, Philippe-Emmanuel Mangeot, Mournetas, Virginie, Nectoux, Juliette, Deburgrave, Nathalie, Nusbaum, Patrick, Leturcq, France, Popplewell, Linda, Dickson, George, Wein, Nicolas, Flanigan, Kevin, Peschanski, Marc, Chelly, Jamel, and Pinset, Christian

Abstract

The new DMD exon 1 belongs to a retrovirus-like sequence. (a) Alignment of the new exon 1 region (highlighted in light blue) among 100 vertebrate species with the conserved upstream/downstream sequence marked by red arrows ( https://genome.ucsc.edu ). (b) Schematic representation of the approximately 8 kb region in the DMD gene that is conserved among a sub-group of anthropoids. It is composed of simple repeats, Alu sequences and the whole human endogenous retrovirus-like sequence HuERS-P1 ( http://www.dfam.org/entry/DF0000214 ) flanked by two LTR8 elements.

Published
2015
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21. Additional file 4: Figure S6. of Dp412e: a novel human embryonic dystrophin isoform induced by BMP4 in early differentiated cells

Author

Massouridès, Emmanuelle, Polentes, Jérôme, Philippe-Emmanuel Mangeot, Mournetas, Virginie, Nectoux, Juliette, Deburgrave, Nathalie, Nusbaum, Patrick, Leturcq, France, Popplewell, Linda, Dickson, George, Wein, Nicolas, Flanigan, Kevin, Peschanski, Marc, Chelly, Jamel, and Pinset, Christian

Abstract

Dystrophin protein expression. (a) Western blot analyses of protein extracts from hiPSCs 1 at day 4 either without or after BMP4 treatment using antibodies directed against different regions of dystrophin. (Dystrophin antibodies: Manex6 (exon 6); Mandys19 (exon 21), Mandys101 (exon 40–41), Manhinge4A (exon 62), Manex7374A (exon 73–74), Mandra1 (exon 77). (b) Western blot with DYS1 antibody in three pluripotent stem cell lines (hiPSCs 2 and 4, hESCs 2) from days 3 through 7 following BMP4 treatment. (c) Quantification of dystrophin protein levels from the Western blots (b) in Fig. 3 and (b) in Fig. S6 (Muscle biopsy protein extract from a healthy individual serves as a control and α-tubulin was used as loading control).

Published
2015
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22. Additional file 9: Figure S7. of Dp412e: a novel human embryonic dystrophin isoform induced by BMP4 in early differentiated cells

Author

Massouridès, Emmanuelle, Polentes, Jérôme, Philippe-Emmanuel Mangeot, Mournetas, Virginie, Nectoux, Juliette, Deburgrave, Nathalie, Nusbaum, Patrick, Leturcq, France, Popplewell, Linda, Dickson, George, Wein, Nicolas, Flanigan, Kevin, Peschanski, Marc, Chelly, Jamel, and Pinset, Christian

Subjects
embryonic structures
Abstract

Dp412e expression study. Fold change obtained by quantitative RT-PCR using primers specific for Dp427m, Dp427c and Dp412e on RNAs from either human adult tissues, 7–11 weeks old fetuses or human 25–40 weeks old fetal tissues. Gene expression was normalized to UBC and relative to BMP4-treated hiPSCs 1 at day 3.

Published
2015
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23. Additional file 6: Figure S2. of Dp412e: a novel human embryonic dystrophin isoform induced by BMP4 in early differentiated cells

Author

Massouridès, Emmanuelle, Polentes, Jérôme, Philippe-Emmanuel Mangeot, Mournetas, Virginie, Nectoux, Juliette, Deburgrave, Nathalie, Nusbaum, Patrick, Leturcq, France, Popplewell, Linda, Dickson, George, Wein, Nicolas, Flanigan, Kevin, Peschanski, Marc, Chelly, Jamel, and Pinset, Christian

Abstract

5′RACE reveals the presence of a novel exon 1. (a, b) Two sequences found several times by 5′RACE PCR on RNA from hiPSCs 1 three days after BMP4 treatment. In black are represented the nucleotides found to be spliced to the DMD gene exon 2 by 5′RACE PCR, with in (a), the 164 last nucleotides of Dp427c exon 1 and in (b), the new exon 1. In red are the parts of the RACE sequence corresponding to DMD gene exon 2. The black box in Dp427c sequence points out a nucleotide that does not match with Dp427c exon 1 reference sequence. The BLAT analyses were done on the web site https://genome.ucsc.edu .

Published
2015
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24. Additional file 3: Figure S5. of Dp412e: a novel human embryonic dystrophin isoform induced by BMP4 in early differentiated cells

Author

Massouridès, Emmanuelle, Polentes, Jérôme, Philippe-Emmanuel Mangeot, Mournetas, Virginie, Nectoux, Juliette, Deburgrave, Nathalie, Nusbaum, Patrick, Leturcq, France, Popplewell, Linda, Dickson, George, Wein, Nicolas, Flanigan, Kevin, Peschanski, Marc, Chelly, Jamel, and Pinset, Christian

Subjects
embryonic structures
Abstract

BMP4-treated hiPSCs/hESCs express dystrophin protein. (a) Western blot in six pluripotent stem cell lines (hiPSCs 1, 3 and 4, DMD hiPSCs 1 and 3, hESCs 2) at day 4 either without or after BMP4 treatment. (b) Western blot in hiPSCs 1 from days 0 through 4 after a single BMP4 treatment. (Dystrophin antibody: DYS1; Muscle biopsy protein extract from a healthy individual serves as a control, α-tubulin was used as loading control).

Published
2015
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25. Additional file 5: Figure S1. of Dp412e: a novel human embryonic dystrophin isoform induced by BMP4 in early differentiated cells

Author

Massouridès, Emmanuelle, Polentes, Jérôme, Philippe-Emmanuel Mangeot, Mournetas, Virginie, Nectoux, Juliette, Deburgrave, Nathalie, Nusbaum, Patrick, Leturcq, France, Popplewell, Linda, Dickson, George, Wein, Nicolas, Flanigan, Kevin, Peschanski, Marc, Chelly, Jamel, and Pinset, Christian

Subjects
musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities
Abstract

BMP4-treated hPSCs express a new transient long DMD transcript. qRT-PCR of DMD transcripts using primers specific to exons 2–3 in hiPSCs 1 and DMD hiPSCs 3 at days 3 through 7 after BMP4 treatment. For each cell line, gene expression was normalized to GAPDH and plotted (log10 scale) relative to the expression at D0.

Published
2015
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26. Additional file 8: Figure S4. of Dp412e: a novel human embryonic dystrophin isoform induced by BMP4 in early differentiated cells

Author

Massouridès, Emmanuelle, Polentes, Jérôme, Philippe-Emmanuel Mangeot, Mournetas, Virginie, Nectoux, Juliette, Deburgrave, Nathalie, Nusbaum, Patrick, Leturcq, France, Popplewell, Linda, Dickson, George, Wein, Nicolas, Flanigan, Kevin, Peschanski, Marc, Chelly, Jamel, and Pinset, Christian

Abstract

In silico translation of the novel DMD transcript. Representation of the open reading frame (ORF) resulting in translation of the novel DMD transcript. Possible translated proteins from this ORF are represented in red. The largest predicted protein is composed of 3562 amino acids (≈412 kDa) ( http://web.expasy.org/translate ).

Published
2015
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27. Additional file 2: Table S2. of Dp412e: a novel human embryonic dystrophin isoform induced by BMP4 in early differentiated cells

Author

Massouridès, Emmanuelle, Polentes, Jérôme, Philippe-Emmanuel Mangeot, Mournetas, Virginie, Nectoux, Juliette, Deburgrave, Nathalie, Nusbaum, Patrick, Leturcq, France, Popplewell, Linda, Dickson, George, Wein, Nicolas, Flanigan, Kevin, Peschanski, Marc, Chelly, Jamel, and Pinset, Christian

Abstract

Primer list. Primers used in the present study.

Published
2015
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28. Additional file 1: Table S1. of Dp412e: a novel human embryonic dystrophin isoform induced by BMP4 in early differentiated cells

Author

Massouridès, Emmanuelle, Polentes, Jérôme, Philippe-Emmanuel Mangeot, Mournetas, Virginie, Nectoux, Juliette, Deburgrave, Nathalie, Nusbaum, Patrick, Leturcq, France, Popplewell, Linda, Dickson, George, Wein, Nicolas, Flanigan, Kevin, Peschanski, Marc, Chelly, Jamel, and Pinset, Christian

Abstract

Human embryonic and induced pluripotent stem cell line list. Details concerning the stem cell lines used in the present study.

Published
2015
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29. Dual mTORC1/2 inhibition induces anti-proliferative effect in NF1-associated plexiform neurofibroma and malignant peripheral nerve sheath tumor cells

Author

Varin, Jennifer, primary, Poulain, Laury, additional, Hivelin, Mikael, additional, Nusbaum, Patrick, additional, Hubas, Arnaud, additional, Laurendeau, Ingrid, additional, Lantieri, Laurent, additional, Wolkenstein, Pierre, additional, Vidaud, Michel, additional, Pasmant, Eric, additional, Chapuis, Nicolas, additional, and Parfait, Béatrice, additional

Published
2016
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30. Dp412e: a novel human embryonic dystrophin isoform induced by BMP4 in early differentiated cells

Author

Massouridès, Emmanuelle, primary, Polentes, Jérôme, additional, Mangeot, Philippe-Emmanuel, additional, Mournetas, Virginie, additional, Nectoux, Juliette, additional, Deburgrave, Nathalie, additional, Nusbaum, Patrick, additional, Leturcq, France, additional, Popplewell, Linda, additional, Dickson, George, additional, Wein, Nicolas, additional, Flanigan, Kevin M., additional, Peschanski, Marc, additional, Chelly, Jamel, additional, and Pinset, Christian, additional

Published
2015
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31. A Thermolabile Aldolase A Mutant Causes Fever-Induced Recurrent Rhabdomyolysis without Hemolytic Anemia

Author

Mamoune, Asmaa, primary, Bahuau, Michel, additional, Hamel, Yamina, additional, Serre, Valérie, additional, Pelosi, Michele, additional, Habarou, Florence, additional, Nguyen Morel, Marie-Ange, additional, Boisson, Bertrand, additional, Vergnaud, Sabrina, additional, Viou, Mai Thao, additional, Nonnenmacher, Luc, additional, Piraud, Monique, additional, Nusbaum, Patrick, additional, Vamecq, Joseph, additional, Romero, Norma, additional, Ottolenghi, Chris, additional, Casanova, Jean-Laurent, additional, and de Lonlay, Pascale, additional

Published
2014
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36. Characterization of a recombinant proteinase 3, the autoantigen in Wegener's granulomatosis and its reactivity with anti‐neutrophil cytoplasmic autoantibodies

Author

Witko-Sarsat, Véronique, primary, Halbwachs-Mecarelli, Lise, additional, Almeida, Roque P., additional, Nusbaum, Patrick, additional, Melchior, Maxine, additional, Jamaleddine, Ghassan, additional, Lesavre, Philippe, additional, Descamps-Latscha, Béatrice, additional, and Gabay, Joëlle E., additional

Published
1996
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38. Apoptosis‐induced proteinase 3 membrane expression is independent from degranulation

Author

Durant, Stéphanie, Pederzoli, Magali, Lepelletier, Yves, Canteloup, Sandrine, Nusbaum, Patrick, Lesavre, Philippe, and Witko‐Sarsat, Véronique

Abstract

Proteinase 3 (PR3) and human neutrophil elastase (HNE) are serine proteinases stored in the azurophilic granules of neutrophils. In contrast to HNE, PR3 is the target of antineutrophil cytoplasm antibodies (ANCA) in Wegener's granulomatosis. The mechanisms leading to the membrane expression of PR3 and HNE are still unclear and appear to be critical to understand the pathophysiological role of ANCA. Stably transfected rat basophilic cell lines (RBL) with PR3 or HNE were used to analyze the PR3 and HNE secretion mechanisms and differentiate between them. RBL cells were lacking endogenous PR3 and HNE. They were stably transfected with HNE or PR3 or an inactive mutant of PR3 (PR3S203A). Using the calcium ionophore A23187 as a secretagogue, higher serine proteinase activity was secreted in the supernatant of RBL/HNE than in RBL/PR3. It is interesting that PR3 and PR3/S203A were also expressed at the plasma membrane, thus demonstrating that serine protease activity was not required for plasma membrane expression. In contrast, no expression of plasma membrane HNE could be detected in RBL/HNE. Apoptosis induced by etoposide was evaluated by DNA fragmentation, the presence of cytoplasmic histone‐associated DNA fragments, and annexin V labeling. No membrane HNE was detected in RBL/HNE. In contrast, in RBL/PR3 and in RBL/PR3S203A, the membrane expression of PR3 and PR3S203A increased with etoposide concentrations and appeared closely related to annexin V labeling. Our data suggest that membrane PR3 originates from two distinct pools, the granular pool mobilized following degranulation or a plasma membrane pool mobilized upon apoptosis.

Published
2004
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39. β4Integrin and Laminin 5 Are Aberrantly Expressed in Polycystic Kidney Disease

Author

Joly, Dominique, Morel, Viviane, Hummel, Aurélie, Ruello, Antonella, Nusbaum, Patrick, Patey, Natacha, Noël, Laure-Hélène, Rousselle, Patricia, and Knebelmann, Bertrand

Abstract

Extracellular matrix alterations have been suggested to be part of the early events occurring in Autosomal Dominant Polycystic Kidney Disease (ADPKD), a disease characterized by formation of renal cysts and progressive renal failure. Here we report that cDNA array analysis identified β4integrin aberrant expression in ADPKD cells. Furthermore, laminin 5 (Ln-5), the main α6β4integrin ligand, was also found to be abnormally expressed in ADPKD. Studies performed with ADPKD cyst-lining epithelial cells (CC) by comparison with normal tubular cells indicate that integrin α6β4-Ln-5 interactions are involved in cellular events of potential importance for cystogenesis: 1) laminin 5 is a preferential adhesion substrate for CC, mainly through α6β4interaction, 2) CC increased haptotactic and chemotactic motility depends on the presence of Ln-5 and requires integrin α3β1cooperation, and 3) CC haptotactic or chemotactic migration is specifically increased by mAb-mediated β4integrin ligation, through an α3β1integrin-dependent and independent pathway, respectively. These results highlight the role of Ln-5 and α6β4integrin in adhesive and motility properties of cyst-lining epithelial cells, and further suggest that integrins and extracellular matrix modifications may be of general relevance to kidney epithelial cell cyst formation.

Published
2003
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40. Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises and no primary energetic defect.

Author

Bérat CM, Montealegre S, Wiedemann A, Nuzum MLC, Blondel A, Debruge H, Cano A, Chabrol B, Hoebeke C, Polak M, Stoupa A, Feillet F, Torre S, Boddaert N, Bruel H, Barth M, Damaj L, Abi-Wardé MT, Afenjar A, Benoist JF, Madrange M, Caccavelli L, Renard P, Hubas A, Nusbaum P, Pontoizeau C, Gobin S, van Endert P, Ottolenghi C, Maltret A, and de Lonlay P

Subjects
Adolescent, Child, Child, Preschool, Exome, Female, France, Humans, Hypothyroidism genetics, Infant, Male, Mitochondria genetics, Mutation, Pedigree, Phenotype, Retrospective Studies, Young Adult, Arrhythmias, Cardiac genetics, Aryl Hydrocarbon Receptor Nuclear Translocator deficiency, Aryl Hydrocarbon Receptor Nuclear Translocator genetics, Neurodevelopmental Disorders genetics, Rhabdomyolysis genetics
Abstract

TANGO2 disease is a severe inherited disorder associating multiple symptoms such as metabolic crises, encephalopathy, cardiac arrhythmias, and hypothyroidism. The mechanism of action of TANGO2 is currently unknown. Here, we describe a cohort of 20 French patients bearing mutations in the TANGO2 gene. We found that the main clinical presentation was the association of neurodevelopmental delay (n = 17), acute metabolic crises (n = 17) and hypothyroidism (n = 12), with a large intrafamilial clinical variability. Metabolic crises included rhabdomyolysis (15/17), neurological symptoms (14/17), and cardiac features (12/17; long QT (n = 10), Brugada pattern (n = 2), cardiac arrhythmia (n = 6)) that required intensive care. We show previously uncharacterized triggers of metabolic crises in TANGO2 patients, such as some anesthetics and possibly l-carnitine. Unexpectedly, plasma acylcarnitines, plasma FGF-21, muscle histology, and mitochondrial spectrometry were mostly normal. Moreover, in patients' primary myoblasts, palmitate and glutamine oxidation rates, and the mitochondrial network were also normal. Finally, we found variable mitochondrial respiration and defective clearance of oxidized DNA upon cycles of starvation and refeeding. We conclude that TANGO2 disease is a life-threatening disease that needs specific cardiac management and anesthesia protocol. Mechanistically, TANGO2 disease is unlikely to originate from a primary mitochondrial defect. Rather, we suggest that mitochondrial defects are secondary to strong extrinsic triggers in TANGO2 deficient patients., (© 2020 SSIEM.)

Published
2021
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41. Beta4 integrin and laminin 5 are aberrantly expressed in polycystic kidney disease: role in increased cell adhesion and migration.

Author

Joly D, Morel V, Hummel A, Ruello A, Nusbaum P, Patey N, Noël LH, Rousselle P, and Knebelmann B

Subjects
Adult, Blotting, Western, Cell Adhesion, Cell Adhesion Molecules genetics, Cell Movement, Cells, Cultured, Epithelial Cells cytology, Epithelial Cells metabolism, Female, Fluorescent Antibody Technique, Humans, Immunohistochemistry, Integrin beta4 genetics, Kidney physiology, Oligonucleotide Array Sequence Analysis, Polycystic Kidney, Autosomal Dominant genetics, Polycystic Kidney, Autosomal Dominant pathology, Reverse Transcriptase Polymerase Chain Reaction, Up-Regulation, Kalinin, Cell Adhesion Molecules biosynthesis, Integrin beta4 biosynthesis, Kidney cytology, Polycystic Kidney, Autosomal Dominant metabolism
Abstract

Extracellular matrix alterations have been suggested to be part of the early events occurring in Autosomal Dominant Polycystic Kidney Disease (ADPKD), a disease characterized by formation of renal cysts and progressive renal failure. Here we report that cDNA array analysis identified beta(4) integrin aberrant expression in ADPKD cells. Furthermore, laminin 5 (Ln-5), the main alpha(6)beta(4) integrin ligand, was also found to be abnormally expressed in ADPKD. Studies performed with ADPKD cyst-lining epithelial cells (CC) by comparison with normal tubular cells indicate that integrin alpha(6)beta(4)-Ln-5 interactions are involved in cellular events of potential importance for cystogenesis: 1) laminin 5 is a preferential adhesion substrate for CC, mainly through alpha(6)beta(4) interaction, 2) CC increased haptotactic and chemotactic motility depends on the presence of Ln-5 and requires integrin alpha(3)beta(1) cooperation, and 3) CC haptotactic or chemotactic migration is specifically increased by mAb-mediated beta(4) integrin ligation, through an alpha(3)beta(1) integrin-dependent and independent pathway, respectively. These results highlight the role of Ln-5 and alpha(6)beta(4) integrin in adhesive and motility properties of cyst-lining epithelial cells, and further suggest that integrins and extracellular matrix modifications may be of general relevance to kidney epithelial cell cyst formation.

Published
2003
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