5 results on '"Geoffroy, Véronique"'
Search Results
2. Mutations inKARScause a severe neurological and neurosensory disease with optic neuropathy
- Author
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Scheidecker, Sophie, primary, Bär, Séverine, additional, Stoetzel, Corinne, additional, Geoffroy, Véronique, additional, Lannes, Béatrice, additional, Rinaldi, Bruno, additional, Fischer, Frédéric, additional, Becker, Hubert D., additional, Pelletier, Valérie, additional, Pagan, Cécile, additional, Acquaviva‐Bourdain, Cécile, additional, Kremer, Stéphane, additional, Mirande, Marc, additional, Tranchant, Christine, additional, Muller, Jean, additional, Friant, Sylvie, additional, and Dollfus, Hélène, additional
- Published
- 2019
- Full Text
- View/download PDF
3. Whole-genome sequencing in patients with ciliopathies uncovers a novel recurrent tandem duplication in IFT140
- Author
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Geoffroy, Véronique, Stoetzel, Corinne, Scheidecker, Sophie, Schaefer, Elise, Perrault, Isabelle, Bär, Séverine, Kröll, Ariane, Delbarre, Marion, Antin, Manuela, Leuvrey, Anne-Sophie, Henry, Charline, Blanché, Hélène, Decker, Eva, Kloth, Katja, Klaus, Günter, Mache, Christoph, Martin-Coignard, Dominique, McGinn, Steven, Boland, Anne, Deleuze, Jean-François, Friant, Sylvie, Saunier, Sophie, Rozet, Jean-Michel, Bergmann, Carsten, Dollfus, Hélène, Muller, Jean, Laboratoire de Génétique Médicale (LGM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Génétique Médicale, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Génétique moléculaire, génomique, microbiologie (GMGM), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Les Hôpitaux Universitaires de Strasbourg (HUS), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Néphropathies héréditaires et rein en développement (UMR_S 983), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris] (CEPH), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Philipps Universität Marburg = Philipps University of Marburg, Medical University of Graz, Centre Hospitalier Le Mans (CH Le Mans), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire des Maladies Rénales Héréditaires = Laboratory of Hereditary Kidney Diseases (Equipe Inserm 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), University Hospital Freiburg, Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale, and Hôpitaux Universitaires de Strasbourg
- Subjects
Male ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Heterozygote ,Cerebellar Ataxia ,Whole Genome Sequencing ,[SDV]Life Sciences [q-bio] ,Homozygote ,copy number variation ,structural variation ,Exons ,Alu-mediated recombination ,Ciliopathies ,Pedigree ,Phenotype ,whole-genome sequencing ,Alu Elements ,IFT140 ,Mainzer-Saldino syndrome ,Databases, Genetic ,Mutation ,tandem duplication ,Humans ,Female ,Carrier Proteins ,Retinitis Pigmentosa - Abstract
International audience; Ciliopathies represent a wide spectrum of rare diseases with overlapping phenotypes and a high genetic heterogeneity. Among those, IFT140 is implicated in a variety of phenotypes ranging from isolated retinis pigmentosa to more syndromic cases. Using whole-genome sequencing in patients with uncharacterized ciliopathies, we identified a novel recurrent tandem duplication of exon 27-30 (6.7 kb) in IFT140, c.3454-488_4182+2588dup p.(Tyr1152_Thr1394dup), missed by whole-exome sequencing. Pathogenicity of the mutation was assessed on the patients' skin fibroblasts. Several hundreds of patients with a ciliopathy phenotype were screened and biallelic mutations were identified in 11 families representing 12 pathogenic variants of which seven are novel. Among those unrelated families especially with a Mainzer-Saldino syndrome, eight carried the same tandem duplication (two at the homozygous state and six at the heterozygous state). In conclusion, we demonstrated the implication of structural variations in IFT140-related diseases expanding its mutation spectrum. We also provide evidences for a unique genomic event mediated by an Alu-Alu recombination occurring on a shared haplotype. We confirm that whole-genome sequencing can be instrumental in the ability to detect structural variants for genomic disorders.
- Published
- 2018
- Full Text
- View/download PDF
4. Novel IQCE variations confirm its role in postaxial polydactyly and cause ciliary defect phenotype in zebrafish.
- Author
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Estrada‐Cuzcano, Alejandro, Etard, Christelle, Delvallée, Clarisse, Stoetzel, Corinne, Schaefer, Elise, Scheidecker, Sophie, Geoffroy, Véronique, Schneider, Aline, Studer, Fouzia, Mattioli, Francesca, Chennen, Kirsley, Sigaudy, Sabine, Plassard, Damien, Poch, Olivier, Piton, Amélie, Strahle, Uwe, Muller, Jean, and Dollfus, Hélène
- Abstract
Polydactyly is one of the most frequent inherited defects of the limbs characterized by supernumerary digits and high‐genetic heterogeneity. Among the many genes involved, either in isolated or syndromic forms, eight have been implicated in postaxial polydactyly (PAP). Among those, IQCE has been recently identified in a single consanguineous family. Using whole‐exome sequencing in patients with uncharacterized ciliopathies, including PAP, we identified three families with biallelic pathogenic variations in IQCE. Interestingly, the c.895_904del (p.Val301Serfs*8) was found in all families without sharing a common haplotype, suggesting a recurrent mechanism. Moreover, in two families, the systemic phenotype could be explained by additional pathogenic variants in known genes (TULP1, ATP6V1B1). RNA expression analysis on patients' fibroblasts confirms that the dysfunction of IQCE leads to the dysregulation of genes associated with the hedgehog‐signaling pathway, and zebrafish experiments demonstrate a full spectrum of phenotypes linked to defective cilia: Body curvature, kidney cysts, left–right asymmetry, misdirected cilia in the pronephric duct, and retinal defects. In conclusion, we identified three additional families confirming IQCE as a nonsyndromic PAP gene. Our data emphasize the importance of taking into account the complete set of variations of each individual, as each clinical presentation could finally be explained by multiple genes. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
5. Mutations in KARS cause a severe neurological and neurosensory disease with optic neuropathy.
- Author
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Scheidecker, Sophie, Bär, Séverine, Stoetzel, Corinne, Geoffroy, Véronique, Lannes, Béatrice, Rinaldi, Bruno, Fischer, Frédéric, Becker, Hubert D., Pelletier, Valérie, Pagan, Cécile, Acquaviva‐Bourdain, Cécile, Kremer, Stéphane, Mirande, Marc, Tranchant, Christine, Muller, Jean, Friant, Sylvie, and Dollfus, Hélène
- Abstract
Mutations in genes encoding aminoacyl‐tRNA synthetases have been reported in several neurological disorders. KARS is a dual localized lysyl‐tRNA synthetase and its cytosolic isoform belongs to the multiple aminoacyl‐tRNA synthetase complex (MSC). Biallelic mutations in the KARS gene were described in a wide phenotypic spectrum ranging from nonsyndromic deafness to complex impairments. Here, we report on a patient with severe neurological and neurosensory disease investigated by whole‐exome sequencing and found to carry biallelic mutations c.683C>T (p.Pro228Leu) and c.871T>G (p.Phe291Val), the second one being novel, in the KARS gene. The patient presented with an atypical clinical presentation with an optic neuropathy not previously reported. At the cellular level, we show that cytoplasmic KARS was expressed at a lower level in patient cells and displayed decreased interaction with MSC. In vitro, these two KARS variants have a decreased aminoacylation activity compared with wild‐type KARS, the p.Pro228Leu being the most affected. Our data suggest that dysfunction of cytoplasmic KARS resulted in a decreased level of translation of the nuclear‐encoded lysine‐rich proteins belonging to the respiratory chain complex, thus impairing mitochondria functions. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
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