Truncated prelamin A expression in HGPS-like patients: a transcriptional study
| Autor: | Martha Spilioti, Eva Morava, Claire Navarro, Nathalie Da Silva, Marc Bartoli, Athanasios Evangeliou, Martine Lemerrer, Sabine Sigaudy, Kyriaki Papadopoulou-Legbelou, Racha Fayek, Patrice Roll, Andrée Robaglia-Schlupp, Florian Barthélémy, Nicolas Lévy, Annachiara De Sandre-Giovannoli, Ron A. Wevers, Gisèle Bonne, Junko Oshima |
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| Přispěvatelé: | Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), Département de génétique médicale [Hôpital de la Timone - APHM], Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), University of Washington [Seattle], Thérapie des maladies du muscle strié, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), School of medicine [Thessaloniki], Aristotle University of Thessaloniki, Head of the Department of Medical Genetics, Department of Environmental Science [Radboud Universiteit Nijmegen, Netherlands], Radboud university [Nijmegen], Department of Pediatrics, University Children's Hospital, Laboratoire de Biologie Cellulaire [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Radboud University [Nijmegen] |
| Rok vydání: | 2015 |
| Předmět: |
Male
Premature aging congenital hereditary and neonatal diseases and abnormalities Transcription Genetic RNA Splicing Biology Article LMNA Exon Progeria Genetics medicine Humans Missense mutation Protein Precursors Genetics (clinical) [SDV.GEN]Life Sciences [q-bio]/Genetics integumentary system Disease genetics nutritional and metabolic diseases Aging Premature Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] Fibroblasts Lamin Type A Progerin medicine.disease Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] Pedigree 3. Good health Gene Expression Regulation Mutation Nuclear lamina Female RNA Splice Sites Lamin |
| Zdroj: | European Journal of Human Genetics European Journal of Human Genetics, Nature Publishing Group, 2015, 23 (8), pp.1051-1061. ⟨10.1038/ejhg.2014.239⟩ European Journal of Human Genetics, 23, 8, pp. 1051-61 European Journal of Human Genetics, 2015, 23 (8), pp.1051-1061. ⟨10.1038/ejhg.2014.239⟩ European Journal of Human Genetics, 23, 1051-61 |
| ISSN: | 1018-4813 1476-5438 |
| DOI: | 10.1038/ejhg.2014.239⟩ |
| Popis: | Contains fulltext : 154354.pdf (Publisher’s version ) (Closed access) Premature aging syndromes are rare genetic disorders mimicking clinical and molecular features of aging. A recently identified group of premature aging syndromes is linked to mutation of the LMNA gene encoding lamins A and C, and is associated with nuclear deformation and dysfunction. Hutchinson-Gilford progeria syndrome (HGPS) was the first premature aging syndrome linked to LMNA mutation and its molecular bases have been deeply investigated. It is due to a recurrent de novo mutation leading to aberrant splicing and the production of a truncated and toxic nuclear lamin A precursor (prelamin ADelta50), also called progerin. In this work and based on the literature data, we propose to distinguish two main groups of premature aging laminopathies: (1) HGPS and HGP-like syndromes, which share clinical features due to hampered processing and intranuclear toxic accumulation of prelamin A isoforms; and (2) APS (atypical progeria syndromes), due to dominant or recessive missense mutations affecting lamins A and C. Among HGPS-like patients, several deleted prelamin A transcripts (prelamin ADelta50, ADelta35 and ADelta90) have been described. The purpose of this work was to characterize those transcripts in eight patients affected with HGP-like rare syndromes. When fibroblasts were available, the relationships between the presence and ratios of these transcripts and other parameters were studied, aiming to increase our understanding of genotype-phenotype relationships in HGPS-like patients. Altogether our results evidence that progerin accumulation is the major pathogenetic mechanism responsible for HGP-like syndromes due to mutations near the donor splice site of exon 11. |
| Databáze: | OpenAIRE |
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