Copy number variations and founder effect underlying complete IL-10Rβ deficiency in Portuguese kindreds
| العنوان: | Copy number variations and founder effect underlying complete IL-10Rβ deficiency in Portuguese kindreds |
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| المؤلفون: | Charbit-Henrion, Fabienne, Bègue, Bernadette, Sierra, Anaïs, Hanein, Sylvain, Stolzenberg, Marie-Claude, Li, Zhi, Pellegrini, Sandra, Garcelon, Nicolas, Jeanpierre, Marc, Neven, Bénédicte, Loge, Isabelle, Picard, Capucine, Rosain, Jeremie, Bustamante, Jacinta, Le Lorc'H, Marc, Pigneur, Benedicte, Fernandes, Alicia, Rieux-Laucat, Frédéric, Amil Dias, Jorge, Ruemmele, Frank, Cerf-Bensussan, Nadine |
| المساهمون: | Laboratory of Intestinal Immunity (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gastroentérologie, d'hépatologie et nutrition pédiatrique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), GENIUS Group, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Signalisation des Cytokines - Cytokine Signaling, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), Service de Génétique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hôpital Charles Nicolle [Rouen], Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], Laboratoire Histologie Embryologie Cytogénétique [CHU Necker], Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centro Hospitalar São João EPE, This work was supported by Institutional grants from INSERM, by the European grant ERC-2013-AdG-339407-IMMUNOBIOTA, by the Investissement d’Avenir grant ANR-10-IAHU-01 and by the Fondation Princesse Grace. FCH was supported by fellowships from Institut Imagine and from INSERM. NCB benefits from an Interface-Assistance Publique-Hôpitaux de Paris. Work by ZL and SP was supported by CNRS and institutional grants from Institut Pasteur and INSERM., GENIUS Group : http://www.genius-group.orgTest, ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), European Project: 339407,EC:FP7:ERC,ERC-2013-ADG,IMMUNOBIOTA(2014), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Li, Zhi, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Host-microbiota interactions across the gut immune system:lessons from early onset inflammatory bowel diseases and from gnotobiotic mice - IMMUNOBIOTA - - EC:FP7:ERC2014-03-01 - 2019-02-28 - 339407 - VALID |
| المصدر: | PLoS ONE PLoS ONE, Public Library of Science, 2018, 13 (10), pp.e0205826. ⟨10.1371/journal.pone.0205826⟩ PLoS ONE, 2018, 13 (10), pp.e0205826. ⟨10.1371/journal.pone.0205826⟩ |
| بيانات النشر: | HAL CCSD, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, Heterozygote, DNA, Complementary, Heredity, DNA Copy Number Variations, [SDV.IMM] Life Sciences [q-bio]/Immunology, Amino Acid Motifs, Gene Identification and Analysis, Artificial Gene Amplification and Extension, [SDV.GEN] Life Sciences [q-bio]/Genetics, Genome Complexity, Research and Analysis Methods, Biochemistry, Polymerase Chain Reaction, Sequencing techniques, Genetics, Humans, DNA sequencing, Post-Translational Modification, Phosphorylation, Frameshift Mutation, Molecular Biology Techniques, Molecular Biology, Mutation Detection, Alleles, Family Health, [SDV.GEN]Life Sciences [q-bio]/Genetics, Portugal, Genome, Human, Homozygote, Infant, Biology and Life Sciences, Computational Biology, Proteins, Exons, Genomics, Interleukin-10 Receptor beta Subunit, Founder Effect, Copy Number Variation, Genetic Mapping, Deletion Mutation, Haplotypes, Mutation, Leukocytes, Mononuclear, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Microsatellite Repeats, Signal Transduction, Research Article |
| الوصف: | International audience; Mutations in interleukin-10 receptor (IL-10R) genes are one cause of very early-onset inflammatory bowel disease with perianal lesions, which can be cured by hematopoietic stem cell transplantation. Using a functional test, which assesses responsiveness of peripheral monocytes to IL-10, we identified three unrelated Portuguese patients carrying two novel IL-10RB mutations. In the three patients, sequencing of genomic DNA identified the same large deletion of exon 3 which precluded protein expression. This mutation was homozygous in two patients born from consanguineous families and heterozygous in the third patient born from unrelated parents. Microsatellite analysis of the IL10RB genomic region revealed a common haplotype in the three Portuguese families pointing to a founder deletion inherited from a common ancestor 400 years ago. In the third patient, surface expression of IL-10R was normal but signaling in response to IL-10 was impaired. Complementary DNA sequencing and next-generation sequencing of IL10RB locus with custom-made probes revealed a ≈ 6 Kb duplication encompassing the exon 6 which leads to a frameshift mutation and a loss of the TYK2-interacting Box 2 motif. Altogether, we describe two novel copy number variations in IL10RB, one with founder effect and one preserving cell surface expression but abolishing signaling. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::3fa2998ffb5ebae35194f90ad2d3f1a9Test https://hal-pasteur.archives-ouvertes.fr/pasteur-02070998Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....3fa2998ffb5ebae35194f90ad2d3f1a9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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