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1. COL4A1/COL4A2 and inherited platelet disorder gene variants in fetuses showing intracranial hemorrhage.

Author

Coste, Thibault, Vincent-Delorme, Catherine, Stichelbout, Morgane, Devisme, Louise, Gelot, Antoinette, Deryabin, Igor, Pelluard, Fanny, Aloui, Chaker, Leutenegger, Anne-Louise, Jouannic, Jean-Marie, Héron, Delphine, Tournier-Lasserve, Elisabeth, and Gould, Douglas

Subjects
Cohort Studies, Collagen Type IV, Fetus, Humans, Infant, Newborn, Intracranial Hemorrhages, Mutation
Abstract

BACKGROUND: Variants of COL4A1/COL4A2 genes have been reported in fetal intracranial hemorrhage (ICH) cases but their prevalence and characteristics have not been established in a large series of fetuses. Fetal neonatal alloimmune thrombocytopenia is a major acquired ICH factor but the prevalence and characteristics of inherited platelet disorder (IPD) gene variants leading to thrombocytopenia are unknown. Herein, we screened COL4A1/COL4A2 and IPD genes in a large series of ICH fetuses. METHODS: A cohort of 194 consecutive ICH fetuses were first screened for COL4A1/COL4A2 variants. We manually curated a list of 64 genes involved in IPD and investigated them in COL4A1/COL4A2 negative fetuses, using exome sequencing data from 101 of these fetuses. RESULT: Pathogenic variants of COL4A1/COL4A2 genes were identified in 36 fetuses (19%). They occurred de novo in 70% of the 32 fetuses for whom parental DNA was available. Pathogenic variants in two megakaryopoiesis genes (MPL and MECOM genes) were identified in two families with recurrent and severe fetal ICH, with variable extraneurological pathological features. CONCLUSION: Our study emphasizes the genetic heterogeneity of fetal ICH and the need to screen both COL4A1/COL4A2 and IPD genes in the etiological investigation of fetal ICH to allow proper genetic counseling.

Published
2022

2. Microglia maintain structural integrity during fetal brain morphogenesis

Author

Lawrence, Akindé René, Canzi, Alice, Bridlance, Cécile, Olivié, Nicolas, Lansonneur, Claire, Catale, Clarissa, Pizzamiglio, Lara, Kloeckner, Benoit, Silvin, Aymeric, Munro, David A.D., Fortoul, Aurélien, Boido, Davide, Zehani, Feriel, Cartonnet, Hugues, Viguier, Sarah, Oller, Guillaume, Squarzoni, Paola, Candat, Adrien, Helft, Julie, Allet, Cécile, Watrin, Francoise, Manent, Jean-Bernard, Paoletti, Pierre, Thieffry, Denis, Cantini, Laura, Pridans, Clare, Priller, Josef, Gélot, Antoinette, Giacobini, Paolo, Ciobanu, Luisa, Ginhoux, Florent, Thion, Morgane Sonia, Lokmane, Ludmilla, and Garel, Sonia

Published
2024
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3. In mice and humans, brain microvascular contractility matures postnatally

Author

Slaoui, Leila, Gilbert, Alice, Rancillac, Armelle, Delaunay-Piednoir, Barbara, Chagnot, Audrey, Gerard, Quentin, Letort, Gaëlle, Mailly, Philippe, Robil, Noémie, Gelot, Antoinette, Lefebvre, Mathilde, Favier, Maryline, Dias, Karine, Jourdren, Laurent, Federici, Laetitia, Auvity, Sylvain, Cisternino, Salvatore, Vivien, Denis, Cohen-Salmon, Martine, and Boulay, Anne-Cécile

Published
2023
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4. Homozygous GRN mutations: unexpected phenotypes and new insights into pathological and molecular mechanisms

Author

Huin, Vincent, Barbier, Mathieu, Bottani, Armand, Lobrinus, Johannes, Clot, Fabienne, Lamari, Foudil, Chat, Laureen, Rucheton, Benoît, Fluchère, Frédérique, Auvin, Stéphane, Myers, Peter, Gelot, Antoinette, Camuzat, Agnès, Caillaud, Catherine, Jornéa, Ludmila, Forlani, Sylvie, Saracino, Dario, Duyckaerts, Charles, Brice, Alexis, Durr, Alexandra, and Ber, Isabelle Le

Subjects
Quantitative Biology - Biomolecules, Quantitative Biology - Genomics, Quantitative Biology - Neurons and Cognition
Abstract

Homozygous mutations in the progranulin gene (GRN) are associated with neuronal ceroid lipofuscinosis 11 (CLN11), a rare lysosomal-storage disorder characterized by cerebellar ataxia, seizures, retinitis pigmentosa, and cognitive disorders, usually beginning between 13 and 25 years of age. This is a rare condition, previously reported in only four families. In contrast, heterozygous GRN mutations are a major cause of frontotemporal dementia associated with neuronal cytoplasmic TDP-43 inclusions. We identified homozygous GRN mutations in six new patients. The phenotypic spectrum is much broader than previously reported, with two remarkably distinct presentations, depending on the age of onset. A childhood/juvenile form is characterized by classical CLN11 symptoms at an early age at onset. Unexpectedly, other homozygous patients presented a distinct delayed phenotype of frontotemporal dementia and parkinsonism after 50 years; none had epilepsy or cerebellar ataxia. Another major finding of this study is that all GRN mutations may not have the same impact on progranulin protein synthesis. A hypomorphic effect of some mutations is supported by the presence of residual levels of plasma progranulin and low levels of normal transcript detected in one case with a homozygous splice-site mutation and late onset frontotemporal dementia. This is a new critical finding that must be considered in therapeutic trials based on replacement strategies. The first neuropathological study in a homozygous carrier provides new insights into the pathological mechanisms of the disease. Hallmarks of neuronal ceroid lipofuscinosis were present. The absence of TDP-43 cytoplasmic inclusions markedly differs from observations of heterozygous mutations, suggesting a pathological shift between lysosomal and TDP-43 pathologies depending on the mono or bi-allelic status. An intriguing observation was the loss of normal TDP-43 staining in the nucleus of some neurons, which could be the first stage of the TDP-43 pathological process preceding the formation of typical cytoplasmic inclusions. Finally, this study has important implications for genetic counselling and molecular diagnosis. Semi-dominant inheritance of GRN mutations implies that specific genetic counseling should be delivered to children and parents of CLN11 patients, as they are heterozygous carriers with a high risk of developing dementia. More broadly, this study illustrates the fact that genetic variants can lead to different phenotypes according to their mono- or bi-allelic state, which is a challenge for genetic diagnosis.

Published
2020
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5. First reports of fetal SMARCC1 related hydrocephalus

Author

Rive Le Gouard, Nicolas, Nicolle, Romain, Lefebvre, Mathilde, Gelot, Antoinette, Heide, Solveig, Gerasimenko, Anna, Grigorescu, Romulus, Derive, Nicolas, Jouannic, Jean-Marie, Garel, Catherine, Valence, Stéphanie, Quenum-Miraillet, Geneviève, Chantot-Bastaraud, Sandra, Keren, Boris, Heron, Delphine, and Attie-Bitach, Tania

Published
2023
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6. Somatic double-hit in MTOR and RPS6 in hemimegalencephaly with intractable epilepsy

Author

Pelorosso, Cristiana, Watrin, Françoise, Conti, Valerio, Buhler, Emmanuelle, Gelot, Antoinette, Yang, Xiaoxu, Mei, Davide, McEvoy-Venneri, Jennifer, Manent, Jean-Bernard, Cetica, Valentina, Ball, Laurel L, Buccoliero, Anna Maria, Vinck, Antonin, Barba, Carmen, Gleeson, Joseph G, Guerrini, Renzo, and Represa, Alfonso

Subjects
Rare Diseases, Neurosciences, Epilepsy, Genetics, Neurodegenerative, Tuberous Sclerosis, Brain Disorders, Pediatric, Aetiology, 2.1 Biological and endogenous factors, Neurological, Animals, Brain, Child, Drug Resistant Epilepsy, Female, Hemimegalencephaly, Humans, Malformations of Cortical Development, Malformations of Cortical Development, Group I, Mice, Mosaicism, Mutation, Neurons, Ribosomal Protein S6, TOR Serine-Threonine Kinases, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Single germline or somatic activating mutations of mammalian target of rapamycin (mTOR) pathway genes are emerging as a major cause of type II focal cortical dysplasia (FCD), hemimegalencephaly (HME) and tuberous sclerosis complex (TSC). A double-hit mechanism, based on a primary germline mutation in one allele and a secondary somatic hit affecting the other allele of the same gene in a small number of cells, has been documented in some patients with TSC or FCD. In a patient with HME, severe intellectual disability, intractable seizures and hypochromic skin patches, we identified the ribosomal protein S6 (RPS6) p.R232H variant, present as somatic mosaicism at ~15.1% in dysplastic brain tissue and ~11% in blood, and the MTOR p.S2215F variant, detected as ~8.8% mosaicism in brain tissue, but not in blood. Overexpressing the two variants independently in animal models, we demonstrated that MTOR p.S2215F caused neuronal migration delay and cytomegaly, while RPS6 p.R232H prompted increased cell proliferation. Double mutants exhibited a more severe phenotype, with increased proliferation and migration defects at embryonic stage and, at postnatal stage, cytomegalic cells exhibiting eccentric nuclei and binucleation, which are typical features of balloon cells. These findings suggest a synergistic effect of the two variants. This study indicates that, in addition to single activating mutations and double-hit inactivating mutations in mTOR pathway genes, severe forms of cortical dysplasia can also result from activating mutations affecting different genes in this pathway. RPS6 is a potential novel disease-related gene.

Published
2019

7. Disruption of NEUROD2 causes a neurodevelopmental syndrome with autistic features via cell-autonomous defects in forebrain glutamatergic neurons

Author

Runge, Karen, Mathieu, Rémi, Bugeon, Stéphane, Lafi, Sahra, Beurrier, Corinne, Sahu, Surajit, Schaller, Fabienne, Loubat, Arthur, Herault, Leonard, Gaillard, Stéphane, Pallesi-Pocachard, Emilie, Montheil, Aurélie, Bosio, Andreas, Rosenfeld, Jill A., Hudson, Eva, Lindstrom, Kristin, Mercimek-Andrews, Saadet, Jeffries, Lauren, van Haeringen, Arie, Vanakker, Olivier, Van Hecke, Audrey, Amrom, Dina, Küry, Sebastien, Ratner, Chana, Jethva, Reena, Gamble, Candace, Jacq, Bernard, Fasano, Laurent, Santpere, Gabriel, Lorente-Galdos, Belen, Sestan, Nenad, Gelot, Antoinette, Giacuzz, Sylvie, Goebbels, Sandra, Represa, Alfonso, Cardoso, Carlos, Cremer, Harold, and de Chevigny, Antoine

Published
2021
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8. Sphingolipid desaturase DEGS1 is essential for mitochondria-associated membrane integrity

Author

Planas-Serra, Laura, Launay, Nathalie, Goicoechea, Leire, Heron, Benedicte, Jou, Cristina, Julia-Palacios, Natalia, Ruiz, Montserrat, Fourcade, Stephane, Casasnovas, Carlos, De La Torre, Carolina, Gelot, Antoinette, Marsal, Maria, Loza- Alvarez, Pablo, Garcia-Cazorla, Angels, Fatemi, Ali, Ferrer, Isidre, Portero-Otin, Manel, Area-Gomez, Estela, and Pujol, Aurora

Subjects
Sphingolipids -- Health aspects -- Physiological aspects, Mitochondrial membranes -- Physiological aspects -- Health aspects, Endoplasmic reticulum -- Health aspects -- Physiological aspects, Enzymes -- Health aspects -- Physiological aspects, Metabolism, Inborn errors of -- Causes of -- Genetic aspects, Lipid metabolism -- Health aspects -- Genetic aspects, Health care industry
Abstract

Sphingolipids function as membrane constituents and signaling molecules, with crucial roles in human diseases, from neurodevelopmental disorders to cancer, best exemplified in the inborn errors of sphingolipid metabolism in lysosomes. The dihydroceramide desaturase A4-dihydroceramide desaturase 1 (DEGS1) acts in the last step of a sector of the sphingolipid pathway, de novo ceramide biosynthesis. Defects in DEGS1 cause the recently described hypomyelinating leukodystrophy-18 (HLD18) (OMIM #618404). Here, we reveal that DEGS1 is a mitochondria-associated endoplasmic reticulum membrane-resident (MAM-resident) enzyme, refining previous reports locating DEGS1 at the endoplasmic reticulum only. Using patient fibroblasts, multiomics, and enzymatic assays, we show that DEGS1 deficiency disrupts the main core functions of the MAM: (a) mitochondrial dynamics, with a hyperfused mitochondrial network associated with decreased activation of dynamin-related protein 1; (b) cholesterol metabolism, with impaired sterol O- acyltransferase activity and decreased cholesteryl esters; (c) phospholipid metabolism, with increased phosphatidic acid and phosphatidylserine and decreased phosphatidylethanolamine; and (d) biogenesis of lipid droplets, with increased size and numbers. Moreover, we detected increased mitochondrial superoxide species production in fibroblasts and mitochondrial respiration impairment in patient muscle biopsy tissues. Our findings shed light on the pathophysiology of HLD18 and broaden our understanding of the role of sphingolipid metabolism in MAM function., Introduction Sphingolipids (SLs) are fundamental components of cellular membranes and bioactive signaling molecules that are constituted by a sphingoid base backbone coupled to a fatty acyl chain. Ceramide (Cer) serves [...]

Published
2023
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9. Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction

Author

Akizu, Naiara, Cantagrel, Vincent, Zaki, Maha S, Al-Gazali, Lihadh, Wang, Xin, Rosti, Rasim Ozgur, Dikoglu, Esra, Gelot, Antoinette Bernabe, Rosti, Basak, Vaux, Keith K, Scott, Eric M, Silhavy, Jennifer L, Schroth, Jana, Copeland, Brett, Schaffer, Ashleigh E, Gordts, Philip LSM, Esko, Jeffrey D, Buschman, Matthew D, Field, Seth J, Napolitano, Gennaro, Abdel-Salam, Ghada M, Ozgul, R Koksal, Sagıroglu, Mahmut Samil, Azam, Matloob, Ismail, Samira, Aglan, Mona, Selim, Laila, Mahmoud, Iman G, Abdel-Hadi, Sawsan, Badawy, Amera El, Sadek, Abdelrahim A, Mojahedi, Faezeh, Kayserili, Hulya, Masri, Amira, Bastaki, Laila, Temtamy, Samia, Müller, Ulrich, Desguerre, Isabelle, Casanova, Jean-Laurent, Dursun, Ali, Gunel, Murat, Gabriel, Stacey B, de Lonlay, Pascale, and Gleeson, Joseph G

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Brain Disorders, Clinical Research, Animals, Atrophy, Autophagy, Cerebellar Diseases, Cerebellum, Child, Preschool, Female, Gene Frequency, Humans, Infant, Lod Score, Lysosomal Storage Diseases, Lysosomes, Male, Mutation, Phagosomes, Sorting Nexins, Spinocerebellar Ataxias, Syndrome, Zebrafish, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology, Genetics
Abstract

Pediatric-onset ataxias often present clinically as developmental delay and intellectual disability, with prominent cerebellar atrophy as a key neuroradiographic finding. Here we describe a new clinically distinguishable recessive syndrome in 12 families with cerebellar atrophy together with ataxia, coarsened facial features and intellectual disability, due to truncating mutations in the sorting nexin gene SNX14, encoding a ubiquitously expressed modular PX domain-containing sorting factor. We found SNX14 localized to lysosomes and associated with phosphatidylinositol (3,5)-bisphosphate, a key component of late endosomes/lysosomes. Patient-derived cells showed engorged lysosomes and a slower autophagosome clearance rate upon autophagy induction by starvation. Zebrafish morphants for snx14 showed dramatic loss of cerebellar parenchyma, accumulation of autophagosomes and activation of apoptosis. Our results characterize a unique ataxia syndrome due to biallelic SNX14 mutations leading to lysosome-autophagosome dysfunction.

Published
2015

10. Correction: Disruption of NEUROD2 causes a neurodevelopmental syndrome with autistic features via cell-autonomous defects in forebrain glutamatergic neurons

Author

Runge, Karen, Mathieu, Rémi, Bugeon, Stéphane, Lafi, Sahra, Beurrier, Corinne, Sahu, Surajit, Schaller, Fabienne, Loubat, Arthur, Herault, Leonard, Gaillard, Stéphane, Pallesi-Pocachard, Emilie, Montheil, Aurélie, Bosio, Andreas, Rosenfeld, Jill A., Hudson, Eva, Lindstrom, Kristin, Mercimek-Andrews, Saadet, Jeffries, Lauren, van Haeringen, Arie, Vanakker, Olivier, Van Hecke, Audrey, Amrom, Dina, Küry, Sebastien, Ratner, Chana, Jethva, Reena, Gamble, Candace, Jacq, Bernard, Fasano, Laurent, Santpere, Gabriel, Lorente-Galdos, Belen, Sestan, Nenad, Gelot, Antoinette, Giacuzz, Sylvie, Goebbels, Sandra, Represa, Alfonso, Cardoso, Carlos, Cremer, Harold, and de Chevigny, Antoine

Published
2021
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11. New recessive mutations in SYT2 causing severe presynaptic congenital myasthenic syndromes

Author

Bauché, Stéphanie, Sureau, Alain, Sternberg, Damien, Rendu, John, Buon, Céline, Messéant, Julien, Boëx, Myriam, Furling, Denis, Fauré, Julien, Latypova, Xénia, Gelot, Antoinette Bernabe, Mayer, Michèle, Mary, Pierre, Whalen, Sandra, Fournier, Emmanuel, Cloix, Isabelle, Remerand, Ganaelle, Laffargue, Fanny, Nougues, Marie-Christine, Fontaine, Bertrand, Eymard, Bruno, Isapof, Arnaud, and Strochlic, Laure

Published
2020
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16. A recurrent de novo splice site variant involving DNM1 exon 10a causes developmental and epileptic encephalopathy through a dominant-negative mechanism

Author

Parthasarathy, Shridhar, primary, Ruggiero, Sarah McKeown, additional, Gelot, Antoinette, additional, Soardi, Fernanda C, additional, Ribeiro, Bethânia F R, additional, Pires, Douglas E V, additional, Ascher, David B, additional, Schmitt, Alain, additional, Rambaud, Caroline, additional, Represa, Alfonso, additional, Xie, Hongbo M, additional, Lusk, Laina, additional, Wilmarth, Olivia, additional, McDonnell, Pamela Pojomovsky, additional, Juarez, Olivia A, additional, Grace, Alexandra N, additional, Buratti, Julien, additional, Mignot, Cyril, additional, Gras, Domitille, additional, Nava, Caroline, additional, Pierce, Samuel R, additional, Keren, Boris, additional, Kennedy, Benjamin C, additional, Pena, Sergio D J, additional, Helbig, Ingo, additional, and Cuddapah, Vishnu Anand, additional

Published
2022
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17. In mice and humans, brain microvascular contractility matures postnatally

Author

Slaoui, Leila, primary, Gilbert, Alice, additional, Rancillac, Armelle, additional, Delaunay-Piednoir, Barbara, additional, Chagnot, Audrey, additional, Gerard, Quentin, additional, Letort, Gaëlle, additional, Mailly, Philippe, additional, Robil, Noémie, additional, Gelot, Antoinette, additional, Lefebvre, Mathilde, additional, Favier, Maryline, additional, Dias, Karine, additional, Jourdren, Laurent, additional, Federici, Laetitia, additional, Auvity, Sylvain, additional, Cisternino, Salvatore, additional, Vivien, Denis, additional, Cohen-Salmon, Martine, additional, and Boulay, Anne-Cécile, additional

Published
2022
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18. Editorial: What does human pathology bring to the understanding of the fundamental mechanisms of development?

Author

Represa, Alfonso, Martínez, Salvador, Gelot, Antoinette, Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto de Neurociencias de Alicante, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), CHU Trousseau [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Cellular and Molecular Neuroscience, Neuroscience (miscellaneous), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Anatomy
Abstract

Editorial on the Research Topic.

Published
2022

19. La panencéphalite sclérosante subaiguë de la rougeole

Author

Lebon, Pierre, Gelot, Antoinette, Zhang, Shen-Ying, Casanova, Jean-Laurent, Hauw, Jean-Jacques, Université Paris Cité (UPCité), Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Rockefeller University [New York], Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), St. Giles Laboratory of Human Genetics of Infectious Diseases, Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, and NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience; Subacute sclerosing panencephalitis, a late complication of measles, is still present during epidemics of this disease due to insufficient vaccination. After a historical review, the importance of the diagnostic criteria and the pathophysiology of SSEP are discussed. Numerous studies on the parameters of innate immunity and interferon responses tend to show a decrease in the activity of cellular immunity. Several hypotheses are formulated based on the publications of the different forms of the disease: Congenital, perinatal, forms with short incubation similar to acute inclusion encephalitis (AIE), rapidly evolving forms, forms of the immunocompromised, or even adults. Familial forms have been identified, suggesting a genetic cause. Based on the duration of the latency period, two groups have been individualized, prompting a retrospective and prospective analysis of the exomes of these patients. The knowledge of the genes involved should be useful for the understanding of the pathophysiology of SSPE and other late neurological RNA virus infections.; La panencéphalite sclérosante subaiguë (PESS), une complication tardive de la rougeole, est encore présente lors d’épidémies de cette maladie dues aux insuffisances de la vaccination. Après un rappel historique, nous aborderons la physiopathologie de la PESS et l’importance des critères diagnostiques. De nombreux travaux portant sur les paramètres de l’immunité innée et sur ceux des réponses interféron tendent à montrer une baisse de l’activité de l’immunité cellulaire au cours de cette maladie. Nous formulons ici plusieurs hypothèses s’appuyant sur des publications concernant différentes formes de la maladie : congénitales, périnatales, formes à incubation courte, semblables à l’encéphalite aiguë à inclusions (EAI), formes d’évolution rapide, formes retrouvées chez les immunodéprimés ou chez l’adulte. Des formes familiales ont également été identifiées, suggérant une origine génétique. Selon la durée de la période de latence entre rougeole et la PESS, deux groupes de patients ont été individualisés, incitant à des analyses rétrospective et prospective des exomes de ces malades. La connaissance des gènes participant à la maladie devrait être utile pour la compréhension de la physiopathologie de la PESS mais aussi d’autres infections neurologiques tardives dues à des virus à ARN.

Published
2022

22. WDR81 mutations cause extreme microcephaly and impair mitotic progression in human fibroblasts and Drosophila neural stem cells

Author

Cavallin, Mara, Rujano, Maria A., Bednarek, Nathalie, Medina-Cano, Daniel, Bernabe Gelot, Antoinette, Drunat, Severine, Maillard, Camille, Garfa-Traore, Meriem, Bole, Christine, Nitschké, Patrick, Beneteau, Claire, Besnard, Thomas, Cogné, Benjamin, Eveillard, Marion, Kuster, Alice, Poirier, Karine, Verloes, Alain, Martinovic, Jelena, Bidat, Laurent, Rio, Marlene, Lyonnet, Stanislas, Reilly, M. Louise, Boddaert, Nathalie, Jenneson-Liver, Melanie, Motte, Jacques, Doco-Fenzy, Martine, Chelly, Jamel, Attie-Bitach, Tania, Simons, Matias, Cantagrel, Vincent, Passemard, Sandrine, Baffet, Alexandre, Thomas, Sophie, and Bahi-Buisson, Nadia

Published
2017
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23. In mice and humans, brain microvascular contractility matures postnatally Brain microvessel post-natal maturation

Author

Slaoui, Leila, primary, Gilbert, Alice, additional, Rancillac, Armelle, additional, Chagnot, Audrey, additional, Federici, Laetitia, additional, Gerard, Quentin, additional, Gelot, Antoinette, additional, Becmeur-Lefebvre, Mathilde, additional, Favier, Maryline, additional, Robil, Noémie, additional, Letort, Gaëlle, additional, Dias, Karine, additional, Jourdren, Laurent, additional, Mailly, Philippe, additional, Auvity, Sylvain, additional, Cisternino, Salvatore, additional, Vivien, Denis, additional, Cohen-Salmon, Martine, additional, and Boulay, Anne-Cécile, additional

Published
2022
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24. Recessive PRDM13 mutations cause fatal perinatal brainstem dysfunction with cerebellar hypoplasia and disrupt Purkinje cell differentiation

Author

Coolen, Marion, primary, Altin, Nami, additional, Rajamani, Karthyayani, additional, Pereira, Eva, additional, Siquier-Pernet, Karine, additional, Puig Lombardi, Emilia, additional, Moreno, Nadjeda, additional, Barcia, Giulia, additional, Yvert, Marianne, additional, Laquerrière, Annie, additional, Pouliet, Aurore, additional, Nitschké, Patrick, additional, Boddaert, Nathalie, additional, Rausell, Antonio, additional, Razavi, Féréchté, additional, Afenjar, Alexandra, additional, Billette de Villemeur, Thierry, additional, Al-Maawali, Almundher, additional, Al-Thihli, Khalid, additional, Baptista, Julia, additional, Beleza-Meireles, Ana, additional, Garel, Catherine, additional, Legendre, Marine, additional, Gelot, Antoinette, additional, Burglen, Lydie, additional, Moutton, Sébastien, additional, and Cantagrel, Vincent, additional

Published
2022
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25. In Mice and Humans, Brain Vascular Barrier Homeostasis and Contractility Are Acquired Postnatally

Author

Slaoui, Leila, primary, Gilbert, Alice, additional, Federici, Laetitia, additional, Rancillac, Armelle, additional, Chagnot, Audrey, additional, Gerard, Quentin, additional, Gelot, Antoinette, additional, Favier, Maryline, additional, Robil, Noémie, additional, Letort, Gaëlle, additional, Dias, Karine, additional, Jourdren, Laurent, additional, Mailly, Philippe, additional, Auvity, Sylvain, additional, Vivien, Denis, additional, Cisternino, Salvatore, additional, Cohen-Salmon, Martine, additional, and Boulay, Anne-Cécile, additional

Published
2022
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26. Identification of a new splice site mutation in synaptotagmin-2 responsible for a severe and early presynaptic form of congenital myasthenic syndrome

Author

Bauché, Stéphanie, Sternberg, Damien, Buon, Céline, Messéant, Julien, Boëx, Myriam, Gelot, Antoinette-Bernabe, Mayer, Michèle, Furling, Denis, Nouguès, Marie-Christine, Eymard, Bruno, Isapof, Arnaud, strochlic, laure, Sureau, Alain, Fontaine, Bertrand, Rendu, John, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Filière Neuromusculaire (FILNEMUS), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche de l'Institut Curie [Paris], Institut Curie [Paris], Biochimie et Genetique Moleculaire, CHU Grenoble, Centre de génétique moléculaire (CGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), and Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)

Subjects
CMS, [SDV]Life Sciences [q-bio], NMJ, minigene, synaptotagmin2
Abstract

International audience; Congenital myasthenic syndromes (CMS) are a clinically and genetically heterogeneous group of inherited disorders caused by defective synaptic transmission at the neuromuscular junction (NMJ) and characterized by fluctuation of muscle weakness and fatigability. Recently, many mutations encoding presynaptic and ubiquitous proteins have been identified as responsible for increasingly complex CMS phenotypes of CMS. Among them, this is the case of autosomal dominant mutations in Synaptotagmin2 (SYT2) C2B domain that have been linked to described as responsible for presynaptic CMS combined to Lambert-Eaton myasthenic syndromes and motor neuropathy forms. SYT2 is the major synaptotagmin isoform expressed at the NMJ and acts as a calcium sensor that is mediated by the presence of two tandem C2 domains. In the French cohort of CMS patients, we recently identified in a consanguineous family a new homozygote recessive intronic mutation in SYT2 causing an early and severe presynaptic CMS. Using a minigene construct we demonstrated that this intronic mutation in the donor splice site of SYT2 intron 4 leads to a SYT2 in-frame exon 4 skipping suppressing the N-terminal part of C2A domain. Morphological and functional studies revealed that defects in SYT2 C2A domain affects NMJs maintenance, synaptic transmission and triggers a decrease of SYT2 expression partially compensated by the upregulation of SYT1 expression at the NMJ. This study reports the identification of a new severe presynaptic CMS form associated to a recessive intronic mutation in SYT2 and completes the previously reported data on the dominant SYT2-related motor neuropathy and Lambert-Eaton myasthenic syndrome.

Published
2021

28. Dysregulation of the NRG1/ERBB pathway causes a developmental disorder with gastrointestinal dysmotility in humans

Author

Le, Thuy Linh, Galmiche, Louise, Levy, Jonathan, Suwannarat, Pim, Hellebrekers, Debby M.E.I., Morarach, Khomgrit, Boismoreau, Franck, Theunissen, Tom E.J., Lefebvre, Mathilde, Pelet, Anna, Martinovic, Jelena, Gelot, Antoinette, Guimiot, Fabien, Calleroz, Amanda, Gitiaux, Cyril, Hully, Marie, Goulet, Olivier, Chardot, Christophe, Drunat, Severine, Capri, Yline, Bole-Feysot, Christine, Nitschké, Patrick, Whalen, Sandra, Mouthon, Linda, Babcock, Holly E., Hofstra, Robert, de Coo, Irenaeus F.M., Tabet, Anne Claude, Molina, Thierry J., Keren, Boris, Brooks, Alice, Smeets, Hubert J.M., Marklund, Ulrika, Gordon, Christopher T., Lyonnet, Stanislas, Amiel, Jeanne, Bondurand, Nadège, Le, Thuy Linh, Galmiche, Louise, Levy, Jonathan, Suwannarat, Pim, Hellebrekers, Debby M.E.I., Morarach, Khomgrit, Boismoreau, Franck, Theunissen, Tom E.J., Lefebvre, Mathilde, Pelet, Anna, Martinovic, Jelena, Gelot, Antoinette, Guimiot, Fabien, Calleroz, Amanda, Gitiaux, Cyril, Hully, Marie, Goulet, Olivier, Chardot, Christophe, Drunat, Severine, Capri, Yline, Bole-Feysot, Christine, Nitschké, Patrick, Whalen, Sandra, Mouthon, Linda, Babcock, Holly E., Hofstra, Robert, de Coo, Irenaeus F.M., Tabet, Anne Claude, Molina, Thierry J., Keren, Boris, Brooks, Alice, Smeets, Hubert J.M., Marklund, Ulrika, Gordon, Christopher T., Lyonnet, Stanislas, Amiel, Jeanne, and Bondurand, Nadège

Abstract

Hirschsprung disease (HSCR) is the most frequent developmental anomaly of the enteric nervous system, with an incidence of 1 in 5000 live births. Chronic intestinal pseudo-obstruction (CIPO) is less frequent and classified as neurogenic or myogenic. Isolated HSCR has an oligogenic inheritance with RET as the major disease-causing gene, while CIPO is genetically heterogeneous, caused by mutations in smooth muscle-specific genes. Here, we describe a series of patients with developmental disorders including gastrointestinal dysmotility, and investigate the underlying molecular bases. Trio-exome sequencing led to the identification of biallelic variants in ERBB3 and ERBB2 in 8 individuals variably associating HSCR, CIPO, peripheral neuropathy, and arthrogryposis. Thorough gut histology revealed aganglionosis, hypoganglionosis, and intestinal smooth muscle abnormalities. The cell type-specific ErbB3 and ErbB2 function was further analyzed in mouse single-cell RNA sequencing data and in a conditional ErbB3-deficient mouse model, revealing a primary role for ERBB3 in enteric progenitors. The consequences of the identified variants were evaluated using quantitative real-time PCR (RT-qPCR) on patient-derived fibroblasts or immunoblot assays on Neuro-2a cells overexpressing WT or mutant proteins, revealing either decreased expression or altered phosphorylation of the mutant receptors. Our results demonstrate that dysregulation of ERBB3 or ERBB2 leads to a broad spectrum of developmental anomalies, including intestinal dysmotility.

Published
2021

29. Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis multiplex congenita with axoglial defects

Author

Laquérriere, Annie, Maluenda, Jérome, Camus, Adrien, Fontenas, Laura, Dieterich, Klaus, Nolent, Flora, Zhou, Jié, Monnier, Nicole, Latour, Philippe, Gentil, Damien, Héron, Delphine, Desguerres, Isabelle, Landrieu, Pierre, Beneteau, Claire, Delaporte, Benoit, Bellesme, Céline, Baumann, Clarisse, Capri, Yline, Goldenberg, Alice, Lyonnet, Stanislas, Bonneau, Dominique, Estournet, Brigitte, Quijano-Roy, Susana, Francannet, Christine, Odent, Sylvie, Saint-Frison, Marie-Hélène, Sigaudy, Sabine, Figarella-Branger, Dominique, Gelot, Antoinette, Mussini, Jean-Marie, Lacroix, Catherine, Drouin-Garraud, Valerie, Malinge, Marie-Claire, Attié-Bitach, Tania, Bessieres, Bettina, Bonniere, Maryse, Encha-Razavi, Ferechte, Beaufrère, Anne-Marie, Khung-Savatovsky, Suonary, Perez, Marie José, Vasiljevic, Alexandre, Mercier, Sandra, Roume, Joelle, Trestard, Laetitia, Saugier-Veber, Pascale, Cordier, Marie-Pierre, Layet, Valérie, Legendre, Marine, Vigouroux-Castera, Adeline, Lunardi, Joel, Bayes, Monica, Jouk, Pierre S., Rigonnot, Luc, Granier, Michèle, Sternberg, Damien, Warszawski, Josiane, Gut, Ivo, Gonzales, Marie, Tawk, Marcel, and Melki, Judith

Published
2014
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30. Megalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit

Author

Gilbert, Alice, primary, Elorza-Vidal, Xabier, additional, Rancillac, Armelle, additional, Chagnot, Audrey, additional, Yetim, Mervé, additional, Hingot, Vincent, additional, Deffieux, Thomas, additional, Boulay, Anne-Cécile, additional, Alvear-Perez, Rodrigo, additional, Cisternino, Salvatore, additional, Martin, Sabrina, additional, Taib, Sonia, additional, Gelot, Antoinette, additional, Mignon, Virginie, additional, Favier, Maryline, additional, Brunet, Isabelle, additional, Declèves, Xavier, additional, Tanter, Mickael, additional, Estevez, Raul, additional, Vivien, Denis, additional, Saubaméa, Bruno, additional, and Cohen-Salmon, Martine, additional

Published
2021
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31. In mice and humans, the brain’s blood vessels mature postnatally to acquire barrier and contractile properties

Author

Slaoui, Leila, primary, Gilbert, Alice, additional, Federici, Laetitia, additional, Rancillac, Armelle, additional, Gelot, Antoinette, additional, Favier, Maryline, additional, Robil, Noémie, additional, Letort, Gaëlle, additional, Dias, Karine, additional, Jourdren, Laurent, additional, Mailly, Philippe, additional, Auvity, Sylvain, additional, Cisternino, Salvatore, additional, Cohen-Salmon, Martine, additional, and Boulay, Anne-Cécile, additional

Published
2021
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33. Dysregulation of the NRG1/ERBB pathway causes a developmental disorder with gastrointestinal dysmotility in humans

Author

Le, Thuy-Linh, primary, Galmiche, Louise, additional, Levy, Jonathan, additional, Suwannarat, Pim, additional, Hellebrekers, Debby M.E.I., additional, Morarach, Khomgrit, additional, Boismoreau, Franck, additional, Theunissen, Tom E.J., additional, Lefebvre, Mathilde, additional, Pelet, Anna, additional, Martinovic, Jelena, additional, Gelot, Antoinette, additional, Guimiot, Fabien, additional, Calleroz, Amanda, additional, Gitiaux, Cyril, additional, Hully, Marie, additional, Goulet, Olivier, additional, Chardot, Christophe, additional, Drunat, Severine, additional, Capri, Yline, additional, Bole-Feysot, Christine, additional, Nitschké, Patrick, additional, Whalen, Sandra, additional, Mouthon, Linda, additional, Babcock, Holly E., additional, Hofstra, Robert, additional, de Coo, Irenaeus F.M., additional, Tabet, Anne-Claude, additional, Molina, Thierry J., additional, Keren, Boris, additional, Brooks, Alice, additional, Smeets, Hubert J.M., additional, Marklund, Ulrika, additional, Gordon, Christopher T., additional, Lyonnet, Stanislas, additional, Amiel, Jeanne, additional, and Bondurand, Nadège, additional

Published
2021
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34. Astrocyte responses after neonatal ischemia: the yin and the yang

Author

Villapol, Sonia, Gelot, Antoinette, Renolleau, Sylvain, and Charriaut-Marlangue, Christiane

Subjects
Infants (Newborn) -- Diseases, Ischemia -- Research -- Diagnosis, Astrocytes -- Research, Psychology and mental health, Diagnosis, Research
Abstract

Byline: Sonia Villapol (Universite Pierre et Marie Curie); Antoinette Gelot (Service de Neuropediatrie, APHP, Hopital Armand Trousseau, Paris, France); Sylvain Renolleau (Universite Pierre et Marie Curie, Service de Reanimation Neonatale [...]

Published
2008
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35. Progression of Fetal Brain Lesions in Tuberous Sclerosis Complex

Author

Gelot, Antoinette Bernabe and Represa, Alfonso

Subjects
interneurons, General Neuroscience, tubers, dysmorphic neurons, development, Giant cells, Neuroscience, Original Research
Abstract

Tuberous sclerosis (TSC) is a multisystem autosomal dominant genetic disorder due to loss of function of TSC1/TSC2 resulting in increased mTOR (mammalian target of rapamycin) signaling. In the brain, TSC is characterized by the formation of specific lesions that include subependymal and white matter nodules and cortical tubers. Cells that constitute TSC lesions are mainly Giant cells and dysmorphic neurons and astrocytes, but normal cells also populate the tubers. Although considered as a developmental disorder, the histopathological features of brain lesions have been described in only a limited number of fetal cases, providing little information on how these lesions develop. In this report we characterized the development of TSC lesions in 14 fetal brains ranging from 19 gestational weeks (GW) to term and 2 postnatal cases. The study focused on the telencephalon at the level of the caudothalamic notch. Our data indicate that subcortical lesions, forming within and at the vicinity of germinative zones, are the first alterations (already detected in 19GW brains), characterized by the presence of numerous dysmorphic astrocytes and Giant, balloon-like, cells. Our data show that cortical tuber formation is a long process that initiates with the presence of dysmorphic astrocytes (by 19–21GW), progress with the apparition of Giant cells (by 24GW) and mature with the appearance of dysmorphic neurons by the end of gestation (by 36GW). Furthermore, the typical tuberal aspect of cortical lesions is only reached when bundles of neurofilament positive extensions delineate the bottom of the cortical lesion (by 36GW). In addition, our study reveals the presence of Giant cells and dysmorphic neurons immunopositive for interneuron markers such as calbindin and parvalbumin, suggesting that TSC lesions would be mosaic lesions generated from different classes of progenitors.

Published
2020
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36. Homozygous GRN mutations: unexpected phenotypes and new insights into pathological and molecular mechanisms: New insights in homozygous GRN mutations

Author

Huin, Vincent, Barbier, Mathieu, Bottani, Armand, Lobrinus, Johannes, Clot, Fabienne, Lamari, Foudil, Chat, Laureen, Rucheton, Benoît, Fluchère, Frédérique, Auvin, Stéphane, Myers, Peter, Gelot, Antoinette, Camuzat, Agnès, Caillaud, Catherine, Jornéa, Ludmila, Forlani, Sylvie, Saracino, Dario, Duyckaerts, Charles, Brice, Alexis, Durr, Alexandra, Le Ber, Isabelle, HUIN, Vincent, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Geneva University Hospital (HUG), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Service de neurologie pédiatrique et maladies métaboliques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Cité (UPCité), Medical Office [Geneva, Switzerland], Service de pathologie [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neuropathologie [CHU Pitié Salpêtrière], and Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A)

Subjects
MESH: Epilepsy / genetics, TDP-43, MESH: Neuronal Ceroid-Lipofuscinoses / diagnostic imaging, MESH: TDP-43 Proteinopathies / physiopathology, MESH: RNA Splicing / genetics, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Child, MESH: Cerebellar Ataxia / genetics, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Cerebellar ataxia, MESH: Heterozygote, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Middle Aged, Neuronal ceroid lipofuscinosis, MESH: Neuronal Ceroid-Lipofuscinoses / physiopathology, MESH: Parkinsonian Disorders / genetics, frontotemporal lobar degeneration, MESH: Cognitive Dysfunction / genetics, MESH: Young Adult, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Parkinsonian Disorders / diagnostic imaging, MESH: TDP-43 Proteinopathies / genetics, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Neuronal Ceroid-Lipofuscinoses / genetics, GRN, Frontotemporal dementia, MESH: Homozygote, MESH: Progranulins / metabolism, MESH: Rare Diseases, Progranulin, MESH: Mutation, MESH: Frontotemporal Dementia / genetics, MESH: Age of Onset, MESH: Parkinsonian Disorders / physiopathology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, MESH: Frontotemporal Dementia / diagnostic imaging, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Retinitis Pigmentosa / genetics, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], MESH: Adolescent, MESH: Humans, MESH: Progranulins / genetics, MESH: Adult, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: TDP-43 Proteinopathies / diagnostic imaging, MESH: Male, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: Frontotemporal Dementia / physiopathology, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Homozygous mutations in the progranulin gene (GRN) are associated with neuronal ceroid lipofuscinosis 11 (CLN11), a rare lysosomal-storage disorder characterized by cerebellar ataxia, seizures, retinitis pigmentosa, and cognitive disorders, usually beginning between 13 and 25 years of age. This is a rare condition, previously reported in only four families. In contrast, heterozygous GRN mutations are a major cause of frontotemporal dementia associated with neuronal cytoplasmic TDP-43 inclusions. We identified homozygous GRN mutations in six new patients. The phenotypic spectrum is much broader than previously reported, with two remarkably distinct presentations, depending on the age of onset. A childhood/juvenile form is characterized by classical CLN11 symptoms at an early age at onset. Unexpectedly, other homozygous patients presented a distinct delayed phenotype of frontotemporal dementia and parkinsonism after 50 years; none had epilepsy or cerebellar ataxia. Another major finding of this study is that all GRN mutations may not have the same impact on progranulin protein synthesis. A hypomorphic effect of some mutations is supported by the presence of residual levels of plasma progranulin and low levels of normal transcript detected in one case with a homozygous splice-site mutation and late onset frontotemporal dementia. This is a new critical finding that must be considered in therapeutic trials based on replacement strategies. The first neuropathological study in a homozygous carrier provides new insights into the pathological mechanisms of the disease. Hallmarks of neuronal ceroid lipofuscinosis were present. The absence of TDP-43 cytoplasmic inclusions markedly differs from observations of heterozygous mutations, suggesting a pathological shift between lysosomal and TDP-43 pathologies depending on the mono or bi-allelic status. An intriguing observation was the loss of normal TDP-43 staining in the nucleus of some neurons, which could be the first stage of the TDP-43 pathological process preceding the formation of typical cytoplasmic inclusions. Finally, this study has important implications for genetic counselling and molecular diagnosis. Semi-dominant inheritance of GRN mutations implies that specific genetic counseling should be delivered to children and parents of CLN11 patients, as they are heterozygous carriers with a high risk of developing dementia. More broadly, this study illustrates the fact that genetic variants can lead to different phenotypes according to their mono- or bi-allelic state, which is a challenge for genetic diagnosis.

Published
2020

38. Gaucher disease

Author

Mignot, Cyril, primary, Gelot, Antoinette, additional, and De Villemeur, Thierry Billette, additional

Published
2013
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39. Congenital glutamine deficiency with glutamine synthetase mutations

Author

Haberle, Johannes, Gorg, Boris, Rutsch, Frank, Schmidt, Eva, Toutain, Annick, Benoist, Jean-Francois, Gelot, Antoinette, uc, Annie-Laure, Hohne, Wolfgang, Schliess, Freimut, Haussinger, Dieter, and Koch, Hans G.

Subjects
Glutamine -- Research, Gene mutations -- Research, Cognition in infants -- Research
Abstract

A report is presented on two unrelated new-borns affected by congenital human glutamine synthetase deficiency with acute brain deformities, which cause multi-organ failure and neonatal mortality. Studies employing immortalized lymphocytes indicate that these mutations are related to minimized glutamine synthetase activity.

Published
2005

40. MFN2, a new gene responsible for mitochondrial DNA depletion

Author

Renaldo, Florence, Amati-Bonneau, Patrizia, Slama, Abdelhamid, Romana, Claudia, Forin, Veronique, Doummar, Diane, Barnerias, Christine, Bursztyn, Joseph, Mayer, Michèle, Khouri, Nejib, Billette de Villemeur, Thierry, Burglen, Lydie, Reynier, Pascal, Bernabe Gelot, Antoinette, and Rodriguez, Diana

Published
2012
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43. Infantile Alexander disease: spectrum of GFAP mutations and genotype-phenotype correlation. (Report)

Author

Rodriguez, Diana, Gauthier, Fernande, Bertini, Enrico, Bugiani, Marianna, Brenner, Michael, N'guyen, Sylvie, Goizet, Cyril, Gelot, Antoinette, Surtees, Robert, Pedespan, Jean-Michel, Hernandorena, Xavier, Troncoso, Monica, Uziel, Graziela, Messing, Albee, Ponsot, Gerard, Pham-Dinh, Danielle, Dautigny, Andre, and Boespflug-Tanguy, Odile

Subjects
Peripheral nerve diseases -- Genetic aspects, Gene mutations -- Analysis, Genetic markers -- Analysis, Mosaicism -- Diagnosis, Biological sciences
Published
2001

44. Mitochondrial dysfunction caused by novel ATAD3A mutations

Author

Dorison, Nathalie, primary, Gaignard, Pauline, additional, Bayot, Aurélien, additional, Gelot, Antoinette, additional, Becker, Pierre Hadrien, additional, Fourati, Salma, additional, Lebigot, Elise, additional, Charles, Perrine, additional, Wai, Timothy, additional, Therond, Patrice, additional, and Slama, Abdelhamid, additional

Published
2020
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46. Homozygous GRN mutations: new phenotypes and new insights into pathological and molecular mechanisms

Author

Huin, Vincent, primary, Barbier, Mathieu, additional, Bottani, Armand, additional, Lobrinus, Johannes Alexander, additional, Clot, Fabienne, additional, Lamari, Foudil, additional, Chat, Laureen, additional, Rucheton, Benoît, additional, Fluchère, Frédérique, additional, Auvin, Stéphane, additional, Myers, Peter, additional, Gelot, Antoinette, additional, Camuzat, Agnès, additional, Caillaud, Catherine, additional, Jornéa, Ludmila, additional, Forlani, Sylvie, additional, Saracino, Dario, additional, Duyckaerts, Charles, additional, Brice, Alexis, additional, Durr, Alexandra, additional, and Le Ber, Isabelle, additional

Published
2019
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47. A novel CNS gene required for neuronal migration and involved in x-linked subcortical laminar heterotopia and lissencephaly syndrome

Author

Portes, Vincent des, Pinard, Jean Marc, Billuart, Pierre, Vinet, Marie Claude, Koulakoff, Annette, Carrie, Alain, Gelot, Antoinette, Dupuis, Elisabeth, Motte, Jacques, Berwald-Netter, Yoheved, Catala, Martin, Kahn, Axel, Beldijord, Cherif, and Chelly, Jamel

Subjects
Central nervous system -- Genetic aspects, Neurons -- Research, Strabismus -- Research, Cells -- Physiological aspects, Brain -- Physiological aspects, Biological sciences
Abstract

Research was conducted to investigate the cloning of a central nervous system gene that was highly characterized in developing brain and neuronal cells that encoded for Doublecortin, a 40 kDa predicted protein. Total RNA was determined from lymphoblastoid cell lines using the guanidium thiocyanate method. Results indicated that presence of a transcript at very high fetal brain level. They also suggested the use of at least four genes to function in the transport of neurons during cortical histogenesis.

Published
1998

50. Paediatric‐onset neuronal ceroid lipofuscinosis: first symptoms and presentation at diagnosis

Author

Dozières‐Puyravel, Blandine, primary, Nasser, Hala, additional, Elmaleh‐Bergès, Monique, additional, Lopez Hernandez, Elisa, additional, Gelot, Antoinette, additional, Ilea, Adina, additional, Delanoë, Catherine, additional, Puech, Jean‐Philippe, additional, Caillaud, Catherine, additional, Pichard, Samia, additional, and Auvin, Stéphane, additional

Published
2019
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