Search

Your search keyword '"Scheidecker, Sophie"' showing total 129 results
Start Over Author "Scheidecker, Sophie"

Refine your results

more »

more »

more »

more »
129 results on '"Scheidecker, Sophie"'

1. Copy Number Variation and Epilepsy: State of the Art in the Era of High-Throughput Sequencing—A Multicenter Cohort Study

Author

Baer, Sarah, Schalk, Audrey, Miguet, Marguerite, Schaefer, Élise, El Chehadeh, Salima, Ginglinger, Emmanuelle, de Saint Martin, Anne, Abi Wardé, Marie-Thérèse, Laugel, Vincent, de Feraudy, Yvan, Gauer, Lucas, Hirsch, Edouard, Boulay, Clotilde, Bansept, Claire, Bolocan, Anamaria, Kitadinis, Ismini, Gouronc, Aurélie, Gérard, Bénédicte, Piton, Amélie, and Scheidecker, Sophie

Published
2024
Full Text
View/download PDF

4. Mutations in TUBGCP4 Alter Microtubule Organization via the γ-Tubulin Ring Complex in Autosomal-Recessive Microcephaly with Chorioretinopathy

Author

Scheidecker, Sophie, Etard, Christelle, Haren, Laurence, Stoetzel, Corinne, Hull, Sarah, Arno, Gavin, Plagnol, Vincent, Drunat, Séverine, Passemard, Sandrine, Toutain, Annick, Obringer, Cathy, Koob, Mériam, Geoffroy, Véronique, Marion, Vincent, Strähle, Uwe, Ostergaard, Pia, Verloes, Alain, Merdes, Andreas, Moore, Anthony T, and Dollfus, Hélène

Subjects
Intellectual and Developmental Disabilities (IDD), Congenital Structural Anomalies, Rare Diseases, Brain Disorders, Neurosciences, Genetics, Clinical Research, Eye Disease and Disorders of Vision, Pediatric, 2.1 Biological and endogenous factors, Aetiology, Eye, Base Sequence, Choroid Diseases, Exome, Eye Diseases, Hereditary, Frameshift Mutation, France, Gene Components, Humans, Microcephaly, Microtubule-Associated Proteins, Microtubules, Molecular Sequence Data, Pedigree, Retinal Diseases, Sequence Analysis, DNA, Tubulin, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

We have identified TUBGCP4 variants in individuals with autosomal-recessive microcephaly and chorioretinopathy. Whole-exome sequencing performed on one family with two affected siblings and independently on another family with one affected child revealed compound-heterozygous mutations in TUBGCP4. Subsequent Sanger sequencing was performed on a panel of individuals from 12 French families affected by microcephaly and ophthalmic manifestations, and one other individual was identified with compound-heterozygous mutations in TUBGCP4. One synonymous variant was common to all three families and was shown to induce exon skipping; the other mutations were frameshift mutations and a deletion. TUBGCP4 encodes γ-tubulin complex protein 4, a component belonging to the γ-tubulin ring complex (γ-TuRC) and known to regulate the nucleation and organization of microtubules. Functional analysis of individual fibroblasts disclosed reduced levels of the γ-TuRC, altered nucleation and organization of microtubules, abnormal nuclear shape, and aneuploidy. Moreover, zebrafish treated with morpholinos against tubgcp4 were found to have reduced head volume and eye developmental anomalies with chorioretinal dysplasia. In summary, the identification of TUBGCP4 mutations in individuals with microcephaly and a spectrum of anomalies in eye development, particularly photoreceptor anomalies, provides evidence of an important role for the γ-TuRC in brain and eye development.

Published
2015

5. Exome sequencing of Bardet–Biedl syndrome patient identifies a null mutation in the BBSome subunit BBIP1 (BBS18)

Author

Scheidecker, Sophie, Etard, Christelle, Pierce, Nathan W, Geoffroy, Véronique, Schaefer, Elise, Muller, Jean, Chennen, Kirsley, Flori, Elisabeth, Pelletier, Valérie, Poch, Olivier, Marion, Vincent, Stoetzel, Corinne, Strähle, Uwe, Nachury, Maxence V, and Dollfus, Hélène

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Rare Diseases, Clinical Research, Congenital Structural Anomalies, Neurodegenerative, Intellectual and Developmental Disabilities (IDD), Pediatric, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Animals, Bardet-Biedl Syndrome, Base Sequence, Carrier Proteins, Codon, Nonsense, Consanguinity, DNA Mutational Analysis, Exome, Fibroblasts, Genetic Association Studies, Genetic Linkage, HEK293 Cells, Humans, Male, Middle Aged, Molecular Sequence Annotation, Pedigree, Phenotype, Polymorphism, Single Nucleotide, Zebrafish, Clinical Genetics, Diagnostics Tests, Genetic Screening, Counselling, Molecular Genetics, Ophthalmology, Genetic Screening/Counselling, Medical and Health Sciences, Genetics & Heredity, Clinical sciences
Abstract

BackgroundBardet-Biedl syndrome (BBS) is a recessive and genetically heterogeneous ciliopathy characterised by retinitis pigmentosa, obesity, kidney dysfunction, postaxial polydactyly, behavioural dysfunction and hypogonadism. 7 of the 17 BBS gene products identified to date assemble together with the protein BBIP1/BBIP10 into the BBSome, a protein complex that ferries signalling receptors to and from cilia.Methods and resultsExome sequencing performed on a sporadic BBS case revealed for the first time a homozygous stop mutation (NM_001195306: c.173T>G, p.Leu58*) in the BBIP1 gene. This mutation is pathogenic since no BBIP1 protein could be detected in fibroblasts from the patient, and BBIP1[Leu58*] is unable to associate with the BBSome subunit BBS4.ConclusionsThese findings identify BBIP1 as the 18th BBS gene (BBS18) and suggest that BBSome assembly may represent a unifying pathomechanism for BBS.

Published
2014

6. Cat eye syndrome: Clinical, cytogenetics and familial findings in a large cohort of 43 patients highlighting the importance of congenital heart disease and inherited cases.

Author

Jedraszak, Guillaume, Jobic, Florence, Receveur, Aline, Bilan, Frédéric, Gilbert‐Dussardier, Brigitte, Tiffany, Busa, Missirian, Chantal, Willems, Marjolaine, Odent, Sylvie, Lucas, Josette, Dubourg, Christele, Schaefer, Elise, Scheidecker, Sophie, Lespinasse, James, Goldenberg, Alice, Guerrot, Anne‐Marie, Joly‐Helas, Géraldine, Chambon, Pascal, Le Caignec, Cédric, and David, Albert

Abstract

Cat Eye Syndrome (CES) is a rare genetic disease caused by the presence of a small supernumerary marker chromosome derived from chromosome 22, which results in a partial tetrasomy of 22p‐22q11.21. CES is classically defined by association of iris coloboma, anal atresia, and preauricular tags or pits, with high clinical and genetic heterogeneity. We conducted an international retrospective study of patients carrying genomic gain in the 22q11.21 chromosomal region upstream from LCR22‐A identified using FISH, MLPA, and/or array‐CGH. We report a cohort of 43 CES cases. We highlight that the clinical triad represents no more than 50% of cases. However, only 16% of CES patients presented with the three signs of the triad and 9% not present any of these three signs. We also highlight the importance of other impairments: cardiac anomalies are one of the major signs of CES (51% of cases), and high frequency of intellectual disability (47%). Ocular motility defects (45%), abdominal malformations (44%), ophthalmologic malformations (35%), and genitourinary tract defects (32%) are other frequent clinical features. We observed that sSMC is the most frequent chromosomal anomaly (91%) and we highlight the high prevalence of mosaic cases (40%) and the unexpectedly high prevalence of parental transmission of sSMC (23%). Most often, the transmitting parent has mild or absent features and carries the mosaic marker at a very low rate (<10%). These data allow us to better delineate the clinical phenotype associated with CES, which must be taken into account in the cytogenetic testing for this syndrome. These findings draw attention to the need for genetic counseling and the risk of recurrence. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

7. Cat eye syndrome: Clinical, cytogenetics and familial findings in a large cohort of 43 patients highlighting the importance of congenital heart disease and inherited cases

Author

Jedraszak, Guillaume, primary, Jobic, Florence, additional, Receveur, Aline, additional, Bilan, Frédéric, additional, Gilbert‐Dussardier, Brigitte, additional, Tiffany, Busa, additional, Missirian, Chantal, additional, Willems, Marjolaine, additional, Odent, Sylvie, additional, Lucas, Josette, additional, Dubourg, Christele, additional, Schaefer, Elise, additional, Scheidecker, Sophie, additional, Lespinasse, James, additional, Goldenberg, Alice, additional, Guerrot, Anne‐Marie, additional, Joly‐Helas, Géraldine, additional, Chambon, Pascal, additional, Le Caignec, Cédric, additional, David, Albert, additional, Coutton, Charles, additional, Satre, Véronique, additional, Vieville, Gaëlle, additional, Amblard, Florence, additional, Harbuz, Radu, additional, Sanlaville, Damien, additional, Till, Marianne, additional, Vincent‐Delorme, Catherine, additional, Colson, Cindy, additional, Andrieux, Joris, additional, Naudion, Sophie, additional, Toutain, Jérome, additional, Rooryck‐Thambo, Caroline, additional, de Fréminville, Bénédicte, additional, Prieur, Fabienne, additional, Daire, Valérie Cormier, additional, Amram, Daniel, additional, Kleinfinger, Pascale, additional, Schulze, Matthias B., additional, Raabe‐Meyer, Gisela, additional, Courage, Carolina, additional, Lemke, Johannes, additional, Stefanou, Eunice G., additional, Loretta, Thomaidis, additional, Emmanouil, Manolakos, additional, Tzeli, Sophia Kitsiou, additional, Sodowska, Henryka, additional, Anderson, Jasen, additional, Nandini, Adayapalam, additional, Copin, Henri, additional, Garçon, Loïc, additional, Liehr, Thomas, additional, and Morin, Gilles, additional

Published
2023
Full Text
View/download PDF

8. Unexpected Inheritance Patterns in a Large Cohort of Patients with a Suspected Ciliopathy

Author

Gouronc, Aurélie, primary, Javey, Elodie, additional, Leuvrey, Anne-Sophie, additional, Nourisson, Elsa, additional, Friedmann, Sylvie, additional, Reichert, Valérie, additional, Derive, Nicolas, additional, Francannet, Christine, additional, Keren, Boris, additional, Lévy, Jonathan, additional, Planes, Marc, additional, Ruaud, Lyse, additional, Amiel, Jeanne, additional, Dollfus, Hélène, additional, Scheidecker, Sophie, additional, and Muller, Jean, additional

Published
2023
Full Text
View/download PDF

9. Proteasome subunit PSMC3 variants cause neurosensory syndrome combining deafness and cataract due to proteotoxic stress

Author

Kröll‐Hermi, Ariane, Ebstein, Frédéric, Stoetzel, Corinne, Geoffroy, Véronique, Schaefer, Elise, Scheidecker, Sophie, Bär, Séverine, Takamiya, Masanari, Kawakami, Koichi, Zieba, Barbara A, Studer, Fouzia, Pelletier, Valerie, Eyermann, Carine, Speeg‐Schatz, Claude, Laugel, Vincent, Lipsker, Dan, Sandron, Florian, McGinn, Steven, Boland, Anne, Deleuze, Jean‐François, Kuhn, Lauriane, Chicher, Johana, Hammann, Philippe, Friant, Sylvie, Etard, Christelle, Krüger, Elke, Muller, Jean, Strähle, Uwe, and Dollfus, Hélène

Published
2020
Full Text
View/download PDF

11. WGS Revealed Novel BBS5 Pathogenic Variants, Missed by WES, Causing Ciliary Structure and Function Defects

Author

Karam, Adella, primary, Delvallée, Clarisse, additional, Estrada-Cuzcano, Alejandro, additional, Geoffroy, Véronique, additional, Lamouche, Jean-Baptiste, additional, Leuvrey, Anne-Sophie, additional, Nourisson, Elsa, additional, Tarabeux, Julien, additional, Stoetzel, Corinne, additional, Scheidecker, Sophie, additional, Porter, Louise Frances, additional, Génin, Emmanuelle, additional, Redon, Richard, additional, Sandron, Florian, additional, Boland, Anne, additional, Deleuze, Jean-François, additional, Le May, Nicolas, additional, Dollfus, Hélène, additional, and Muller, Jean, additional

Published
2023
Full Text
View/download PDF

15. Affected female carriers of MTM1 mutations display a wide spectrum of clinical and pathological involvement: delineating diagnostic clues

Author

Biancalana, Valérie, Scheidecker, Sophie, Miguet, Marguerite, Laquerrière, Annie, Romero, Norma B., Stojkovic, Tanya, Abath Neto, Osorio, Mercier, Sandra, Voermans, Nicol, Tanner, Laura, Rogers, Curtis, Ollagnon-Roman, Elisabeth, Roper, Helen, Boutte, Célia, Ben-Shachar, Shay, Lornage, Xavière, Vasli, Nasim, Schaefer, Elise, Laforet, Pascal, Pouget, Jean, Moerman, Alexandre, Pasquier, Laurent, Marcorelle, Pascale, Magot, Armelle, Küsters, Benno, Streichenberger, Nathalie, Tranchant, Christine, Dondaine, Nicolas, Schneider, Raphael, Gasnier, Claire, Calmels, Nadège, Kremer, Valérie, Nguyen, Karine, Perrier, Julie, Kamsteeg, Erik Jan, Carlier, Pierre, Carlier, Robert-Yves, Thompson, Julie, Boland, Anne, Deleuze, Jean-François, Fardeau, Michel, Zanoteli, Edmar, Eymard, Bruno, and Laporte, Jocelyn

Published
2017
Full Text
View/download PDF

16. Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU

Author

Depienne, Christel, Nava, Caroline, Keren, Boris, Heide, Solveig, Rastetter, Agnès, Passemard, Sandrine, Chantot-Bastaraud, Sandra, Moutard, Marie-Laure, Agrawal, Pankaj B., VanNoy, Grace, Stoler, Joan M., Amor, David J., Billette de Villemeur, Thierry, Doummar, Diane, Alby, Caroline, Cormier-Daire, Valérie, Garel, Catherine, Marzin, Pauline, Scheidecker, Sophie, de Saint-Martin, Anne, Hirsch, Edouard, Korff, Christian, Bottani, Armand, Faivre, Laurence, Verloes, Alain, Orzechowski, Christine, Burglen, Lydie, Leheup, Bruno, Roume, Joelle, Andrieux, Joris, Sheth, Frenny, Datar, Chaitanya, Parker, Michael J., Pasquier, Laurent, Odent, Sylvie, Naudion, Sophie, Delrue, Marie-Ange, Le Caignec, Cédric, Vincent, Marie, Isidor, Bertrand, Renaldo, Florence, Stewart, Fiona, Toutain, Annick, Koehler, Udo, Häckl, Birgit, von Stülpnagel, Celina, Kluger, Gerhard, Møller, Rikke S., Pal, Deb, Jonson, Tord, Soller, Maria, Verbeek, Nienke E., van Haelst, Mieke M., de Kovel, Carolien, Koeleman, Bobby, Monroe, Glen, van Haaften, Gijs, Attié-Bitach, Tania, Boutaud, Lucile, Héron, Delphine, Mignot, Cyril, and DDD Study

Published
2017
Full Text
View/download PDF

17. Clinical and genomic delineation of the new proximal 19p13.3 microduplication syndrome

Author

Jouret, Guillaume, primary, Egloff, Matthieu, additional, Landais, Emilie, additional, Tassy, Olivier, additional, Giuliano, Fabienne, additional, Karmous‐Benailly, Houda, additional, Coutton, Charles, additional, Satre, Véronique, additional, Devillard, Françoise, additional, Dieterich, Klaus, additional, Vieville, Gaëlle, additional, Kuentz, Paul, additional, le Caignec, Cédric, additional, Beneteau, Claire, additional, Isidor, Bertrand, additional, Nizon, Mathilde, additional, Callier, Patrick, additional, Marquet, Valentine, additional, Bieth, Eric, additional, Lévy, Jonathan, additional, Tabet, Anne‐Claude, additional, Lyonnet, Stanislas, additional, Baujat, Geneviève, additional, Rio, Marlène, additional, Cartault, François, additional, Scheidecker, Sophie, additional, Gouronc, Aurélie, additional, Schalk, Audrey, additional, Jacquin, Clémence, additional, Spodenkiewicz, Marta, additional, Angélini, Chloé, additional, Pennamen, Perrine, additional, Rooryck, Caroline, additional, Doco‐Fenzy, Martine, additional, and Poirsier, Céline, additional

Published
2022
Full Text
View/download PDF

18. A Central Role of Telomere Dysfunction in the Formation of a Unique Translocation within the Sub-Telomere Region Resulting in Duplication and Partial Trisomy

Author

M’Kacher, Radhia, primary, Miguet, Marguerite, additional, Maillard, Pierre-Yves, additional, Colicchio, Bruno, additional, Scheidecker, Sophie, additional, Najar, Wala, additional, Arnoux, Micheline, additional, Oudrhiri, Noufissa, additional, Borie, Claire, additional, Biehler, Margaux, additional, Plesch, Andreas, additional, Heidingsfelder, Leonhard, additional, Bennaceur-Griscelli, Annelise, additional, Dieterlen, Alain, additional, Voisin, Philippe, additional, Junker, Steffen, additional, Carde, Patrice, additional, and Jeandidier, Eric, additional

Published
2022
Full Text
View/download PDF

19. 10q26 deletion syndrome: a French cohort study

Author

Thorn, Hugo, Odent, Sylvie, Levy, Jonathan, Tabet, Anne-Claude, Thevenon, Julien, Caignec, Cedric Le, Schaefer, Elise, Frebourg, Thierry, Schluth-Bolard, Caroline, Plutino, Morgane, Chehadeh, Salima El, Philippe, Anais, Scheidecker, Sophie, Calmels, Nadege, Schalk, Audrey, Goldenberg, Alice, Guerot, Anne-Marie, Meur, Nathalie Le, Cassinari, Kevin, Ruaud, Lyse, Rachid, Myriam, Januel, Louis, Bonnet-Dupeyron, Marie-Noëlle, Carneiro, Maryline, Bieth, Eric, Plaisancie, Julie, Coutton, Charles, Harbuz, Radu, Dieterich, Klaus, Nadeau, Gwenaël, Vieville, Gaelle, Fradin, Melanie, Poirsier, Celine, Spodenkiewicz, Marta, Landais, Emilie, Doco-Fenzy, Martine, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Grenoble, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Rouen, Normandie Université (NU), Hospices Civils de Lyon (HCL), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre hospitalier de Valence, Centre Hospitalier Universitaire [Grenoble] (CHU), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Métropole Savoie [Chambéry], CHU Pontchaillou [Rennes], SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA), Wiener Medizinische Akademie GmbH, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), CHU Toulouse [Toulouse], and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)

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

International audience; 10q26 deletion syndrome (OMIM #609625) is a rare autosomal dominant genetic disorder with about 100 patients reported. Most cases are sporadic. Global development delay, short stature, microcephaly and typical facial appearance with triangular face, large forehead, low-set malformed ears, hypertelorism, prominent nose and a thin vermilion of the upper lip constitute the main clinical features. The clinical spectrum is very heterogeneous and neurobehavioral manifestations, deafness, limb malformations, cardiac and urogenital abnormalities can be associated. Thus, patients with 10q26 chromosomal deletion need multidisciplinary management strategies from birth. One of the main reasons for this heterogeneity is the variety of 10qter region chromosomal deletions summarized into the “10q26 deletion syndrome”. Various studies proposed critical regions to explain the main phenotype (Yatzenko et al., 2009; Choucair et al., 2015; Lin S et al., 2016) or more specific features (Vera-Carbonell et al., 2015; Choucair et al., 2015). In addition, these studies proposed about 20 genes of interest such as DOCK1 and FGFR2 to explain the different clinical features observed. We report a French ACLF cohort of 35 patients from 9 centers presenting 10q26 complete or partial deletions (size: 64kb to 12.5Mb), complex chromosomal rearrangement and derivative chromosomes diagnosed using DNA-array, to bring a further insight of the genotype/phenotype correlation.

Published
2022

22. Targeted next‐generation sequencing in a large series of fetuses with severe renal diseases

Author

Jordan, Penelope, primary, Dorval, Guillaume, additional, Arrondel, Christelle, additional, Morinière, Vincent, additional, Tournant, Carole, additional, Audrezet, Marie‐Pierre, additional, Michel‐Calemard, Laurence, additional, Putoux, Audrey, additional, Lesca, Gaethan, additional, Labalme, Audrey, additional, Whalen, Sandra, additional, Loeuillet, Laurence, additional, Martinovic, Jelena, additional, Attie‐Bitach, Tania, additional, Bessières, Bettina, additional, Schaefer, Elise, additional, Scheidecker, Sophie, additional, Lambert, Laetitia, additional, Beneteau, Claire, additional, Patat, Olivier, additional, Boute‐Benejean, Odile, additional, Molin, Arnaud, additional, Guimiot, Fabien, additional, Fontanarosa, Nicolas, additional, Nizon, Mathilde, additional, Lefebvre, Mathilde, additional, Jeanpierre, Cécile, additional, Saunier, Sophie, additional, and Heidet, Laurence, additional

Published
2022
Full Text
View/download PDF

23. A Central Role of Telomere Dysfunction in the Formation of a Unique Translocation within the Sub-Telomere Region Resulting in Duplication and Partial Trisomy.

Author

M'Kacher, Radhia, Miguet, Marguerite, Maillard, Pierre-Yves, Colicchio, Bruno, Scheidecker, Sophie, Najar, Wala, Arnoux, Micheline, Oudrhiri, Noufissa, Borie, Claire, Biehler, Margaux, Plesch, Andreas, Heidingsfelder, Leonhard, Bennaceur-Griscelli, Annelise, Dieterlen, Alain, Voisin, Philippe, Junker, Steffen, Carde, Patrice, and Jeandidier, Eric

Subjects
CHROMOSOMAL translocation, KARYOTYPES, TELOMERES, TRISOMY, CHROMOSOME abnormalities, FLUORESCENCE in situ hybridization, CHROMOSOMAL rearrangement
Abstract

Telomeres play a major role in maintaining genome stability and integrity. Putative involvement of telomere dysfunction in the formation of various types of chromosomal aberrations is an area of active research. Here, we report a case of a six-month-old boy with a chromosomal gain encompassing the 11q22.3q25 region identified by SNP array analysis. The size of the duplication is 26.7 Mb and contains 170 genes (OMIM). The duplication results in partial trisomy of the region in question with clinical consequences, including bilateral renal dysplasia, delayed development, and a heart defect. Moreover, the karyotype determined by R-banding and chromosome painting as well as by hybridization with specific sub-telomere probes revealed the presence of an unbalanced t(9;11)(p24;q22.3) translocation with a unique breakpoint involving the sub-telomere region of the short arm of chromosome 9. The karyotypes of the parents were normal. Telomere integrity in circulating lymphocytes from the child and from his parents was assessed using an automated high-throughput method based on fluorescence in situ hybridization (FISH) with telomere- and centromere-specific PNA probes followed by M-FISH multicolor karyotyping. Very short telomeres, as well as an increased frequency of telomere loss and formation of telomere doublets, were detected in the child's cells. Interestingly, similar telomere profiles were found in the circulating lymphocytes of the father. Moreover, an assessment of clonal telomere aberrations identified chromosomes 9 and 11 with particularly high frequencies of such aberrations. These findings strongly suggest that telomere dysfunction plays a central role in the formation of this specific unbalanced chromosome rearrangement via chromosome end-to-end fusion and breakage–fusion–bridge cycles. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

24. A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet-Biedl syndrome

Author

Delvallée, Clarisse, Nicaise, Samuel, Antin, Manuela, Leuvrey, Anne-Sophie, Nourisson, Elsa, Leitch, Carmen C, Kellaris, Georgios, Stoetzel, Corinne, Geoffroy, Véronique, Scheidecker, Sophie, Keren, Boris, Depienne, Christel, Klar, Joakim, Dahl, Niklas, Deleuze, Jean-François, Génin, Emmanuelle, Redon, Richard, Demurger, Florence, Devriendt, Koenraad, Mathieu-Dramard, Michèle, Poitou-Bernert, Christine, Odent, Sylvie, Katsanis, Nicholas, Mandel, Jean-Louis, Davis, Erica E, Dollfus, Hélène, Muller, Jean, Delvallée, Clarisse, Nicaise, Samuel, Antin, Manuela, Leuvrey, Anne-Sophie, Nourisson, Elsa, Leitch, Carmen C, Kellaris, Georgios, Stoetzel, Corinne, Geoffroy, Véronique, Scheidecker, Sophie, Keren, Boris, Depienne, Christel, Klar, Joakim, Dahl, Niklas, Deleuze, Jean-François, Génin, Emmanuelle, Redon, Richard, Demurger, Florence, Devriendt, Koenraad, Mathieu-Dramard, Michèle, Poitou-Bernert, Christine, Odent, Sylvie, Katsanis, Nicholas, Mandel, Jean-Louis, Davis, Erica E, Dollfus, Hélène, and Muller, Jean

Abstract

Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinitis pigmentosa, obesity, polydactyly, cognitive impairment and renal failure. Pathogenic variants in 24 genes account for the molecular basis of >80% of cases. Toward saturated discovery of the mutational basis of the disorder, we carefully explored our cohorts and identified a hominid-specific SINE-R/VNTR/Alu type F (SVA-F) insertion in exon 13 of BBS1 in eight families. In six families, the repeat insertion was found in trans with c.1169 T > G, p.Met390Arg and in two families the insertion was found in addition to other recessive BBS loci. Whole genome sequencing, de novo assembly and SNP array analysis were performed to characterize the genomic event. This insertion is extremely rare in the general population (found in 8 alleles of 8 BBS cases but not in >10 800 control individuals from gnomAD-SV) and due to a founder effect. Its 2435 bp sequence contains hallmarks of LINE1 mediated retrotransposition. Functional studies with patient-derived cell lines confirmed that the BBS1 SVA-F is deleterious as evidenced by a significant depletion of both mRNA and protein levels. Such findings highlight the importance of dedicated bioinformatics pipelines to identify all types of variation.

Published
2021
Full Text
View/download PDF

26. Proteasome subunit variants cause neurosensory syndrome combining deafness and cataract due to proteotoxic stress

Author

Kröll-Hermi, Ariane, Ebstein, Frédéric, Stoetzel, Corinne, Geoffroy, Véronique, Schaefer, Elise, Scheidecker, Sophie, Bär, Séverine, Takamiya, Masanari, Kawakami, Koichi, Zieba, Barbara A., Studer, Fouzia, Pelletier, Valerie, Eyermann, Carine, Speeg-Schatz, Claude, Laugel, Vincent, Lipsker, Dan, Sandron, Florian, McGinn, Steven, Boland, Anne, Deleuze, Jean-François, Kuhn, Lauriane, Chicher, Johana, Hammann, Philippe, Friant, Sylvie, Etard, Christelle, Krüger, Elke, Muller, Jean, Strähle, Uwe, and Dollfus, Hélène

Subjects
Life sciences, biology, ddc:570
Abstract

The ubiquitin–proteasome system degrades ubiquitin‐modified proteins to maintain protein homeostasis and to control signalling. Whole‐genome sequencing of patients with severe deafness and early‐onset cataracts as part of a neurological, sensorial and cutaneous novel syndrome identified a unique deep intronic homozygous variant in the PSMC3 gene, encoding the proteasome ATPase subunit Rpt5, which lead to the transcription of a cryptic exon. The proteasome content and activity in patient's fibroblasts was however unaffected. Nevertheless, patient's cells exhibited impaired protein homeostasis characterized by accumulation of ubiquitinated proteins suggesting severe proteotoxic stress. Indeed, the TCF11/Nrf1 transcriptional pathway allowing proteasome recovery after proteasome inhibition is permanently activated in the patient's fibroblasts. Upon chemical proteasome inhibition, this pathway was however impaired in patient's cells, which were unable to compensate for proteotoxic stress although a higher proteasome content and activity. Zebrafish modelling for knockout in PSMC3 remarkably reproduced the human phenotype with inner ear development anomalies as well as cataracts, suggesting that Rpt5 plays a major role in inner ear, lens and central nervous system development.

Published
2020
Full Text
View/download PDF

27. A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet‐Biedl syndrome

Author

Delvallée, Clarisse, primary, Nicaise, Samuel, additional, Antin, Manuela, additional, Leuvrey, Anne‐Sophie, additional, Nourisson, Elsa, additional, Leitch, Carmen C., additional, Kellaris, Georgios, additional, Stoetzel, Corinne, additional, Geoffroy, Véronique, additional, Scheidecker, Sophie, additional, Keren, Boris, additional, Depienne, Christel, additional, Klar, Joakim, additional, Dahl, Niklas, additional, Deleuze, Jean‐François, additional, Génin, Emmanuelle, additional, Redon, Richard, additional, Demurger, Florence, additional, Devriendt, Koenraad, additional, Mathieu‐Dramard, Michèle, additional, Poitou‐Bernert, Christine, additional, Odent, Sylvie, additional, Katsanis, Nicholas, additional, Mandel, Jean‐Louis, additional, Davis, Erica E., additional, Dollfus, Hélène, additional, and Muller, Jean, additional

Published
2020
Full Text
View/download PDF

28. Next‐generation sequencing in a series of 80 fetuses with complex cardiac malformations and/or heterotaxy

Author

Liu, Hui, primary, Giguet‐Valard, Anna‐Gaëlle, additional, Simonet, Thomas, additional, Szenker‐Ravi, Emmanuelle, additional, Lambert, Laetitia, additional, Vincent‐Delorme, Catherine, additional, Scheidecker, Sophie, additional, Fradin, Mélanie, additional, Morice‐Picard, Fanny, additional, Naudion, Sophie, additional, Ciorna‐Monferrato, Viorica, additional, Colin, Estelle, additional, Fellmann, Florence, additional, Blesson, Sophie, additional, Jouk, Pierre‐Simon, additional, Francannet, Christine, additional, Petit, Florence, additional, Moutton, Sébastien, additional, Lehalle, Daphné, additional, Chassaing, Nicolas, additional, El Zein, Loubna, additional, Bazin, Anne, additional, Bénéteau, Claire, additional, Attié‐Bitach, Tania, additional, Hanu, Sylvie M., additional, Brechard, Marie‐Pierre, additional, Chiesa, Jean, additional, Pasquier, Laurent, additional, Rooryck, Caroline, additional, Van Maldergem, Lionel, additional, Cabrol, Christelle, additional, El Chehadeh, Salima, additional, Vasiljevic, Alexandre, additional, Isidor, Bertrand, additional, Abel, Carine, additional, Thevenon, Julien, additional, Di Filippo, Sylvie, additional, Vigouroux‐Castera, Adeline, additional, Attia, Jocelyne, additional, Quelin, Chloé, additional, Odent, Sylvie, additional, Piard, Juliette, additional, Giuliano, Fabienne, additional, Putoux, Audrey, additional, Khau Van Kien, Philippe, additional, Yardin, Catherine, additional, Touraine, Renaud, additional, Reversade, Bruno, additional, and Bouvagnet, Patrice, additional

Published
2020
Full Text
View/download PDF

29. High prevalence of Bardet‐Biedl syndrome in La Réunion Island is due to a founder variant in ARL6/BBS3

Author

Gouronc, Aurélie, primary, Zilliox, Vincent, additional, Jacquemont, Marie‐Line, additional, Darcel, Françoise, additional, Leuvrey, Anne‐Sophie, additional, Nourisson, Elsa, additional, Antin, Manuela, additional, Alessandri, Jean‐Luc, additional, Doray, Bérénice, additional, Gueguen, Paul, additional, Payet, Frédérique, additional, Randrianaivo, Hanitra, additional, Stoetzel, Corinne, additional, Scheidecker, Sophie, additional, Flodrops, Hugues, additional, Dollfus, Hélène, additional, and Muller, Jean, additional

Published
2020
Full Text
View/download PDF

30. Expanding the phenotypic spectrum in neurological disorders associated with mutations in KARS gene (lysyl-tRNA synthetase) by the identification of a novel mutation

Author

Scheidecker, Sophie, Bär, Séverine, Stoetzel, Corinne, Geoffroy, Véronique, Lannes, Béatrice, Rinaldi, Bruno, Kremer, Stéphane, Tranchant, Christine, Muller, Jean, Friant, Sylvie, Dollfus, Hélène, Laboratoire de Génétique Médicale (LGM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique moléculaire, génomique, microbiologie (GMGM), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Service de pathologie [CHU Strasbourg], CHU Strasbourg, Service de radiologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, and Friant, Sylvie

Subjects
[SDV] Life Sciences [q-bio], [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV]Life Sciences [q-bio], [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

31. Whole-genome sequencing in patients with ciliopathies uncovers a novel recurrent tandem duplication in IFT140

Author

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

32. Proteasome subunitPSMC3variants cause neurosensory syndrome combining deafness and cataract due to proteotoxic stress

Author

Kröll-Hermi, Ariane, primary, Ebstein, Frédéric, additional, Stoetzel, Corinne, additional, Geoffroy, Véronique, additional, Schaefer, Elise, additional, Scheidecker, Sophie, additional, Bär, Séverine, additional, Takamiya, Masanari, additional, Kawakami, Koichi, additional, Zieba, Barbara A., additional, Studer, Fouzia, additional, Pelletier, Valerie, additional, Speeg-Schatz, Claude, additional, Laugel, Vincent, additional, Lipsker, Dan, additional, Sandron, Florian, additional, McGinn, Steven, additional, Boland, Anne, additional, Deleuze, Jean-François, additional, Kuhn, Lauriane, additional, Chicher, Johana, additional, Hammann, Philippe, additional, Friant, Sylvie, additional, Etard, Christelle, additional, Krüger, Elke, additional, Muller, Jean, additional, Strähle, Uwe, additional, and Dollfus, Hélène, additional

Published
2019
Full Text
View/download PDF

33. NovelIQCEvariations confirm its role in postaxial polydactyly and cause ciliary defect phenotype in zebrafish

Author

Estrada‐Cuzcano, Alejandro, primary, Etard, Christelle, additional, Delvallée, Clarisse, additional, Stoetzel, Corinne, additional, Schaefer, Elise, additional, Scheidecker, Sophie, additional, Geoffroy, Véronique, additional, Schneider, Aline, additional, Studer, Fouzia, additional, Mattioli, Francesca, additional, Chennen, Kirsley, additional, Sigaudy, Sabine, additional, Plassard, Damien, additional, Poch, Olivier, additional, Piton, Amélie, additional, Strahle, Uwe, additional, Muller, Jean, additional, and Dollfus, Hélène, additional

Published
2019
Full Text
View/download PDF

34. Mutations inKARScause a severe neurological and neurosensory disease with optic neuropathy

Author

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

35. HCN1 mutation spectrum: From neonatal epileptic encephalopathy to benign generalized epilepsy and beyond

Author

Genetica Klinische Genetica, Brain, Child Health, Genetica Groep Koeleman, Circulatory Health, Marini, Carla, Porro, Alessandro, Rastetter, Agnès, Dalle, Carine, Rivolta, Ilaria, Bauer, Daniel, Oegema, Renske, Nava, Caroline, Parrini, Elena, Mei, Davide, Mercer, Catherine, Dhamija, Radhika, Chambers, Chelsea, Coubes, Christine, Thévenon, Julien, Kuentz, Paul, Julia, Sophie, Pasquier, Laurent, Dubourg, Christèle, Carré, Wilfrid, Rosati, Anna, Melani, Federico, Pisano, Tiziana, Giardino, Maria, Innes, A. Micheil, Alembik, Yves, Scheidecker, Sophie, Santos, Manuela, Figueiroa, Sonia, Garrido, Cristina, Fusco, Carlo, Frattini, Daniele, Spagnoli, Carlotta, Binda, Anna, Granata, Tiziana, Ragona, Francesca, Freri, Elena, Franceschetti, Silvana, Canafoglia, Laura, Castellotti, Barbara, Gellera, Cinzia, Milanesi, Raffaella, Mancardi, Maria Margherita, Clark, Damien R., Kok, Fernando, Helbig, Katherine L., Ichikawa, Shoji, Sadler, Laurie, Neupauerová, Jana, Laššuthova, Petra, Štěrbová, Katalin, Laridon, Annick, Brilstra, Eva, Koeleman, Bobby, Lemke, Johannes R., Zara, Federico, Striano, Pasquale, Soblet, Julie, Smits, Guillaume, Deconinck, Nicolas, Barbuti, Andrea, Difrancesco, Dario, Leguern, Eric, Guerrini, Renzo, Santoro, Bina, Hamacher, Kay, Thiel, Gerhard, Moroni, Anna, Difrancesco, Jacopo C., Depienne, Christel, Genetica Klinische Genetica, Brain, Child Health, Genetica Groep Koeleman, Circulatory Health, Marini, Carla, Porro, Alessandro, Rastetter, Agnès, Dalle, Carine, Rivolta, Ilaria, Bauer, Daniel, Oegema, Renske, Nava, Caroline, Parrini, Elena, Mei, Davide, Mercer, Catherine, Dhamija, Radhika, Chambers, Chelsea, Coubes, Christine, Thévenon, Julien, Kuentz, Paul, Julia, Sophie, Pasquier, Laurent, Dubourg, Christèle, Carré, Wilfrid, Rosati, Anna, Melani, Federico, Pisano, Tiziana, Giardino, Maria, Innes, A. Micheil, Alembik, Yves, Scheidecker, Sophie, Santos, Manuela, Figueiroa, Sonia, Garrido, Cristina, Fusco, Carlo, Frattini, Daniele, Spagnoli, Carlotta, Binda, Anna, Granata, Tiziana, Ragona, Francesca, Freri, Elena, Franceschetti, Silvana, Canafoglia, Laura, Castellotti, Barbara, Gellera, Cinzia, Milanesi, Raffaella, Mancardi, Maria Margherita, Clark, Damien R., Kok, Fernando, Helbig, Katherine L., Ichikawa, Shoji, Sadler, Laurie, Neupauerová, Jana, Laššuthova, Petra, Štěrbová, Katalin, Laridon, Annick, Brilstra, Eva, Koeleman, Bobby, Lemke, Johannes R., Zara, Federico, Striano, Pasquale, Soblet, Julie, Smits, Guillaume, Deconinck, Nicolas, Barbuti, Andrea, Difrancesco, Dario, Leguern, Eric, Guerrini, Renzo, Santoro, Bina, Hamacher, Kay, Thiel, Gerhard, Moroni, Anna, Difrancesco, Jacopo C., and Depienne, Christel

Published
2018

36. High prevalence of Bardet‐Biedl syndrome in La RéunionIsland is due to a founder variant in ARL6/BBS3.

Author

Gouronc, Aurélie, Zilliox, Vincent, Jacquemont, Marie‐Line, Darcel, Françoise, Leuvrey, Anne‐Sophie, Nourisson, Elsa, Antin, Manuela, Alessandri, Jean‐Luc, Doray, Bérénice, Gueguen, Paul, Payet, Frédérique, Randrianaivo, Hanitra, Stoetzel, Corinne, Scheidecker, Sophie, Flodrops, Hugues, Dollfus, Hélène, and Muller, Jean

Subjects
LAURENCE-Moon-Biedl syndrome, COGNITION disorders, GENETIC counseling, RECESSIVE genes, RETINAL degeneration, FUNCTIONAL analysis
Abstract

Bardet‐Biedl syndrome (BBS) is a rare ciliopathy with variable retinal dystrophy, polydactyly, renal abnormalities, obesity, cognitive impairment, and hypogonadism. Biallelic pathogenic variants have been identified in 24 genes, leading to BBS in an autosomal recessive inheritance pattern. In this study, we investigated a cohort of 16 families (20 individuals) presenting with typical BBS originating from La Réunion Island using sequencing (Sanger and high‐throughput methods) and SNP array. In eight families (12 individuals) we identified the same ARL6/BBS3 variation [c.535G > A, p.(Asp179Asn)]. Bioinformatics and functional analyses revealed an effect of this variant on the splicing of ARL6/BBS3. Owing to the relatively high frequency of this variant, a possible founder effect was suspected. Genotyping of six individuals revealed a common 3.8‐Mb haplotype and estimated the most recent common ancestor to about eight generations confirmed by the known genealogy. Knowledge of this founder effect modifies our diagnostic strategy and enables a personalized genetic counseling for patients from La Réunion Island. Being the first description of BBS patients from La Réunion Island, we could estimate its prevalence between ~1/45000 and ~ 1/66000 individuals. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

37. Novel IQCE variations confirm its role in postaxial polydactyly and cause ciliary defect phenotype in zebrafish.

Author

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

38. HCN1mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond

Author

Marini, Carla, primary, Porro, Alessandro, additional, Rastetter, Agnès, additional, Dalle, Carine, additional, Rivolta, Ilaria, additional, Bauer, Daniel, additional, Oegema, Renske, additional, Nava, Caroline, additional, Parrini, Elena, additional, Mei, Davide, additional, Mercer, Catherine, additional, Dhamija, Radhika, additional, Chambers, Chelsea, additional, Coubes, Christine, additional, Thévenon, Julien, additional, Kuentz, Paul, additional, Julia, Sophie, additional, Pasquier, Laurent, additional, Dubourg, Christèle, additional, Carré, Wilfrid, additional, Rosati, Anna, additional, Melani, Federico, additional, Pisano, Tiziana, additional, Giardino, Maria, additional, Innes, A Micheil, additional, Alembik, Yves, additional, Scheidecker, Sophie, additional, Santos, Manuela, additional, Figueiroa, Sonia, additional, Garrido, Cristina, additional, Fusco, Carlo, additional, Frattini, Daniele, additional, Spagnoli, Carlotta, additional, Binda, Anna, additional, Granata, Tiziana, additional, Ragona, Francesca, additional, Freri, Elena, additional, Franceschetti, Silvana, additional, Canafoglia, Laura, additional, Castellotti, Barbara, additional, Gellera, Cinzia, additional, Milanesi, Raffaella, additional, Mancardi, Maria Margherita, additional, Clark, Damien R, additional, Kok, Fernando, additional, Helbig, Katherine L, additional, Ichikawa, Shoji, additional, Sadler, Laurie, additional, Neupauerová, Jana, additional, Laššuthova, Petra, additional, Štěrbová, Katalin, additional, Laridon, Annick, additional, Brilstra, Eva, additional, Koeleman, Bobby, additional, Lemke, Johannes R, additional, Zara, Federico, additional, Striano, Pasquale, additional, Soblet, Julie, additional, Smits, Guillaume, additional, Deconinck, Nicolas, additional, Barbuti, Andrea, additional, DiFrancesco, Dario, additional, LeGuern, Eric, additional, Guerrini, Renzo, additional, Santoro, Bina, additional, Hamacher, Kay, additional, Thiel, Gerhard, additional, Moroni, Anna, additional, DiFrancesco, Jacopo C, additional, and Depienne, Christel, additional

Published
2018
Full Text
View/download PDF

39. Further delineation of theMECP2duplication syndrome phenotype in 59 French male patients, with a particular focus on morphological and neurological features

Author

Miguet, Marguerite, primary, Faivre, Laurence, additional, Amiel, Jeanne, additional, Nizon, Mathilde, additional, Touraine, Renaud, additional, Prieur, Fabienne, additional, Pasquier, Laurent, additional, Lefebvre, Mathilde, additional, Thevenon, Julien, additional, Dubourg, Christèle, additional, Julia, Sophie, additional, Sarret, Catherine, additional, Remerand, Ganaëlle, additional, Francannet, Christine, additional, Laffargue, Fanny, additional, Boespflug-Tanguy, Odile, additional, David, Albert, additional, Isidor, Bertrand, additional, Vigneron, Jacqueline, additional, Leheup, Bruno, additional, Lambert, Laetitia, additional, Philippe, Christophe, additional, Béri-Dexheimer, Mylène, additional, Cuisset, Jean-Marie, additional, Andrieux, Joris, additional, Plessis, Ghislaine, additional, Toutain, Annick, additional, Guibaud, Laurent, additional, Cormier-Daire, Valérie, additional, Rio, Marlene, additional, Bonnefont, Jean-Paul, additional, Echenne, Bernard, additional, Journel, Hubert, additional, Burglen, Lydie, additional, Chantot-Bastaraud, Sandrine, additional, Bienvenu, Thierry, additional, Baumann, Clarisse, additional, Perrin, Laurence, additional, Drunat, Séverine, additional, Jouk, Pierre-Simon, additional, Dieterich, Klaus, additional, Devillard, Françoise, additional, Lacombe, Didier, additional, Philip, Nicole, additional, Sigaudy, Sabine, additional, Moncla, Anne, additional, Missirian, Chantal, additional, Badens, Catherine, additional, Perreton, Nathalie, additional, Thauvin-Robinet, Christel, additional, AChro-Puce, Réseau, additional, Pedespan, Jean-Michel, additional, Rooryck, Caroline, additional, Goizet, Cyril, additional, Vincent-Delorme, Catherine, additional, Duban-Bedu, Bénédicte, additional, Bahi-Buisson, Nadia, additional, Afenjar, Alexandra, additional, Maincent, Kim, additional, Héron, Delphine, additional, Alessandri, Jean-Luc, additional, Martin-Coignard, Dominique, additional, Lesca, Gaëtan, additional, Rossi, Massimiliano, additional, Raynaud, Martine, additional, Callier, Patrick, additional, Mosca-Boidron, Anne-Laure, additional, Marle, Nathalie, additional, Coutton, Charles, additional, Satre, Véronique, additional, Caignec, Cédric Le, additional, Malan, Valérie, additional, Romana, Serge, additional, Keren, Boris, additional, Tabet, Anne-Claude, additional, Kremer, Valérie, additional, Scheidecker, Sophie, additional, Vigouroux, Adeline, additional, Lackmy-Port-Lis, Marilyn, additional, Sanlaville, Damien, additional, Till, Marianne, additional, Carneiro, Maryline, additional, Gilbert-Dussardier, Brigitte, additional, Willems, Marjolaine, additional, Van Esch, Hilde, additional, Portes, Vincent Des, additional, and El Chehadeh, Salima, additional

Published
2018
Full Text
View/download PDF

40. Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU

Author

Genetica Klinische Genetica, Child Health, Genetica Groep Koeleman, Genetica Groep Van Haaften, Circulatory Health, CMM Sectie Genomics and Bioinformatics, Depienne, Christel, Nava, Caroline, Keren, Boris, Heide, Solveig, Rastetter, Agnès, Passemard, Sandrine, Chantot-Bastaraud, Sandra, Moutard, Marie-Laure, Agrawal, Pankaj B, VanNoy, Grace, Stoler, Joan M, Amor, David J, Billette de Villemeur, Thierry, Doummar, Diane, Alby, Caroline, Cormier-Daire, Valérie, Garel, Catherine, Marzin, Pauline, Scheidecker, Sophie, de Saint-Martin, Anne, Hirsch, Edouard, Korff, Christian, Bottani, Armand, Faivre, Laurence, Verloes, Alain, Orzechowski, Christine, Burglen, Lydie, Leheup, Bruno, Roume, Joelle, Andrieux, Joris, Sheth, Frenny, Datar, Chaitanya, Parker, Michael J, Pasquier, Laurent, Odent, Sylvie, Naudion, Sophie, Delrue, Marie-Ange, Le Caignec, Cédric, Vincent, Marie, Isidor, Bertrand, Renaldo, Florence, Stewart, Fiona, Toutain, Annick, Koehler, Udo, Verbeek, Nienke E, van Haelst, Mieke M, de Kovel, Carolien, Koeleman, Bobby, Monroe, Glen, van Haaften, Gijs, DDD Study, Genetica Klinische Genetica, Child Health, Genetica Groep Koeleman, Genetica Groep Van Haaften, Circulatory Health, CMM Sectie Genomics and Bioinformatics, Depienne, Christel, Nava, Caroline, Keren, Boris, Heide, Solveig, Rastetter, Agnès, Passemard, Sandrine, Chantot-Bastaraud, Sandra, Moutard, Marie-Laure, Agrawal, Pankaj B, VanNoy, Grace, Stoler, Joan M, Amor, David J, Billette de Villemeur, Thierry, Doummar, Diane, Alby, Caroline, Cormier-Daire, Valérie, Garel, Catherine, Marzin, Pauline, Scheidecker, Sophie, de Saint-Martin, Anne, Hirsch, Edouard, Korff, Christian, Bottani, Armand, Faivre, Laurence, Verloes, Alain, Orzechowski, Christine, Burglen, Lydie, Leheup, Bruno, Roume, Joelle, Andrieux, Joris, Sheth, Frenny, Datar, Chaitanya, Parker, Michael J, Pasquier, Laurent, Odent, Sylvie, Naudion, Sophie, Delrue, Marie-Ange, Le Caignec, Cédric, Vincent, Marie, Isidor, Bertrand, Renaldo, Florence, Stewart, Fiona, Toutain, Annick, Koehler, Udo, Verbeek, Nienke E, van Haelst, Mieke M, de Kovel, Carolien, Koeleman, Bobby, Monroe, Glen, van Haaften, Gijs, and DDD Study

Published
2017

41. Mutations in KARS cause a severe neurological and neurosensory disease with optic neuropathy.

Author

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

42. A mutation in VPS15 (PIK3R4) causes a ciliopathy and affects IFT20 release from the cis-Golgi

Author

Stoetzel, Corinne, primary, Bär, Séverine, additional, De Craene, Johan-Owen, additional, Scheidecker, Sophie, additional, Etard, Christelle, additional, Chicher, Johana, additional, Reck, Jennifer R., additional, Perrault, Isabelle, additional, Geoffroy, Véronique, additional, Chennen, Kirsley, additional, Strähle, Uwe, additional, Hammann, Philippe, additional, Friant, Sylvie, additional, and Dollfus, Hélène, additional

Published
2016
Full Text
View/download PDF

43. Prenatal diagnosis of focal dermal hypoplasia: Report of three fetuses and review of the literature

Author

Mary, Laura, primary, Scheidecker, Sophie, additional, Kohler, Monique, additional, Lombardi, Maria-Paola, additional, Delezoide, Anne-Lise, additional, Auberger, Elisabeth, additional, Triau, Stéphane, additional, Colin, Estelle, additional, Gerard, Marion, additional, Grzeschik, Karl-Heinz, additional, Dollfus, Hélène, additional, and Antal, Maria Cristina, additional

Published
2016
Full Text
View/download PDF

44. Further delineation of the MECP2duplication syndrome phenotype in 59 French male patients, with a particular focus on morphological and neurological features

Author

Miguet, Marguerite, Faivre, Laurence, Amiel, Jeanne, Nizon, Mathilde, Touraine, Renaud, Prieur, Fabienne, Pasquier, Laurent, Lefebvre, Mathilde, Thevenon, Julien, Dubourg, Christèle, Julia, Sophie, Sarret, Catherine, Remerand, Ganaelle, Francannet, Christine, Laffargue, Fanny, Boespflug-Tanguy, Odile, David, Albert, Isidor, Bertrand, Vigneron, Jacqueline, Leheup, Bruno, Lambert, Laetitia, Philippe, Christophe, Bèèéri-Dexheimer, Mylèène, Cuisset, Jean-Marie, Andrieux, Joris, Plessis, Ghislaine, Toutain, Annick, Guibaud, Laurent, Cormier-Daire, Valèèéérie, Rio, Marlene, Bonnefont, Jean-Paul, Echenne, Bernard, Journel, Hubert, Burglen, Lydie, Chantot-Bastaraud, Sandrine, Bienvenu, Thierry, Baumann, Clarisse, Perrin, Laurence, Drunat, Sèèéééverine, Jouk, Pierre-Simon, Dieterich, Klaus, Devillard, Francoise, Lacombe, Didier, Philip, Nicole, Sigaudy, Sabine, Moncla, Anne, Missirian, Chantal, Badens, Catherine, Perreton, Nathalie, Thauvin-Robinet, Christel, AChro-Puce, Rèèééééseau, Pedespan, Jean-Michel, Rooryck, Caroline, Goizet, Cyril, Vincent-Delorme, Catherine, Duban-Bedu, Bèèééééénèèéééééédicte, Bahi-Buisson, Nadia, Afenjar, Alexandra, Maincent, Kim, Hèèéééééééron, Delphine, Alessandri, Jean-Luc, Martin-Coignard, Dominique, Lesca, Gaetan, Rossi, Massimiliano, Raynaud, Martine, Callier, Patrick, Mosca-Boidron, Anne-Laure, Marle, Nathalie, Coutton, Charles, Satre, Vèèééééééééronique, Caignec, Cèèééééééééédric Le, Malan, Valèèéééééééééérie, Romana, Serge, Keren, Boris, Tabet, Anne-Claude, Kremer, Valèèééééééééééérie, Scheidecker, Sophie, Vigouroux, Adeline, Lackmy-Port-Lis, Marilyn, Sanlaville, Damien, Till, Marianne, Carneiro, Maryline, Gilbert-Dussardier, Brigitte, Willems, Marjolaine, Van Esch, Hilde, Portes, Vincent Des, and El Chehadeh, Salima

Abstract

The Xq28 duplication involving the MECP2gene (MECP2duplication) has been mainly described in male patients with severe developmental delay (DD) associated with spasticity, stereotypic movements and recurrent infections. Nevertheless, only a few series have been published. We aimed to better describe the phenotype of this condition, with a focus on morphological and neurological features. Through a national collaborative study, we report a large French series of 59 affected males with interstitial MECP2duplication. Most of the patients (93%) shared similar facial features, which evolved with age (midface hypoplasia, narrow and prominent nasal bridge, thick lower lip, large prominent ears), thick hair, livedo of the limbs, tapered fingers, small feet and vasomotor troubles. Early hypotonia and global DD were constant, with 21% of patients unable to walk. In patients able to stand, lower limbs weakness and spasticity led to a singular standing habitus: flexion of the knees, broad-based stance with pseudo-ataxic gait. Scoliosis was frequent (53%), such as divergent strabismus (76%) and hypermetropia (54%), stereotypic movements (89%), without obvious social withdrawal and decreased pain sensitivity (78%). Most of the patients did not develop expressive language, 35% saying few words. Epilepsy was frequent (59%), with a mean onset around 7.4 years of age, and often (62%) drug-resistant. Other medical issues were frequent: constipation (78%), and recurrent infections (89%), mainly lung. We delineate the clinical phenotype of MECP2duplication syndrome in a large series of 59 males. Pulmonary hypertension appeared as a cause of early death in these patients, advocating its screening early in life.

Published
2018
Full Text
View/download PDF

45. Exome sequencing of Bardet–Biedl syndrome patient identifies a null mutation in the BBSome subunitBBIP1(BBS18)

Author

Scheidecker, Sophie, primary, Etard, Christelle, additional, Pierce, Nathan W, additional, Geoffroy, Véronique, additional, Schaefer, Elise, additional, Muller, Jean, additional, Chennen, Kirsley, additional, Flori, Elisabeth, additional, Pelletier, Valérie, additional, Poch, Olivier, additional, Marion, Vincent, additional, Stoetzel, Corinne, additional, Strähle, Uwe, additional, Nachury, Maxence V, additional, and Dollfus, Hélène, additional

Published
2013
Full Text
View/download PDF

46. Identification of a novel mutation confirms the implication of IFT172(BBS20)in Bardet–Biedl syndrome

Author

Schaefer, Elise, Stoetzel, Corinne, Scheidecker, Sophie, Geoffroy, Véronique, Prasad, Megana K, Redin, Claire, Missotte, Isabelle, Lacombe, Didier, Mandel, Jean-Louis, Muller, Jean, and Dollfus, Hélène

Abstract

Bardet–Biedl syndrome (BBS; MIM 209900) is a recessive heterogeneous ciliopathy characterized by retinitis pigmentosa (RP), postaxial polydactyly, obesity, hypogonadism, cognitive impairment and kidney dysfunction. So far, 20 BBS genes have been identified, with the last reported ones being found in one or very few families. Whole-exome sequencing was performed in a consanguineous family in which two affected children presented typical BBS features (retinitis pigmentosa, postaxial polydactyly, obesity, hypogonadism and cognitive impairment) without any mutation identified in known BBS genes at the time of the study. We identified a homozygous splice-site mutation (NM_015662.2: c.4428+3A>G) in both affected siblings in the last reported BBS gene, namely, Intraflagellar Transport 172 Homolog (IFT172). Familial mutation segregation was consistent with autosomal recessive inheritance. IFT172mutations were initially reported in Jeune and Mainzer–Saldino syndromes. Recently, mutations have also been found in isolated RP and Bardet–Biedl-like ciliopathy. This is the second report of IFT172mutations in BBS patients validating IFT172as the twentieth BBS gene (BBS20). Moreover, another IFTgene, IFT27, was already associated with BBS, confirming the implication of IFTgenes in the pathogenesis of BBS.

Published
2016
Full Text
View/download PDF

47. 9q22.3 Microdeletion Syndrome with Multiple Basal Cell Carcinomas Treated with Vismodegib: Three Key Messages in One Patient.

Author

KIENY, Alice, KREMER, Valérie, SCHEIDECKER, Sophie, and LIPSKER, Dan

Subjects
DELETION mutation, PHENOTYPES, BASAL cell carcinoma, BASAL cell nevus syndrome, COGNITIVE ability, DIAGNOSIS, PATIENTS, VISMODEGIB
Abstract

The article presents the medical case of a woman with 9q21.33q22.3 microdeletion with phenotypic featurs that are typical of 9q22.3 microdeletion syndrome and multiple basal cell carcinoma (BCC). The patient is diagnosed with Gorlin syndrome (GS) and undergo treatment with vismodegib drug and showed food tolerance and improvement in cognitive function.

Published
2018
Full Text
View/download PDF

48. A mutation in VPS15 (PIK3R4) causes a ciliopathy and affects IFT20 release from the cis-Golgi

Author

Stoetzel, Corinne, B��r, S��verine, De Craene, Johan-Owen, Scheidecker, Sophie, Etard, Christelle, Chicher, Johana, Reck, Jennifer R., Perrault, Isabelle, Geoffroy, V��ronique, Chennen, Kirsley, Str��hle, Uwe, Hammann, Philippe, Friant, Sylvie, and Dollfus, H��l��ne

Subjects
Mechanisms of disease, Ciliogenesis, Disease genetics, Golgi, 10. No inequality
Abstract

Ciliopathies are a group of diseases that affect kidney and retina among other organs. Here, we identify a missense mutation in PIK3R4 (phosphoinositide 3-kinase regulatory subunit 4, named VPS15) in a family with a ciliopathy phenotype. Besides being required for trafficking and autophagy, we show that VPS15 regulates primary cilium length in human fibroblasts, as well as ciliary processes in zebrafish. Furthermore, we demonstrate its interaction with the golgin GM130 and its localization to the Golgi. The VPS15-R998Q patient mutation impairs Golgi trafficking functions in humanized yeast cells. Moreover, in VPS15-R998Q patient fibroblasts, the intraflagellar transport protein IFT20 is not localized to vesicles trafficking to the cilium but is restricted to the Golgi. Our findings suggest that at the Golgi, VPS15 and GM130 form a protein complex devoid of VPS34 to ensure the IFT20-dependent sorting and transport of membrane proteins from the cis-Golgi to the primary cilium.

49. Clinical and genomic delineation of the new proximal 19p13.3 microduplication syndrome.

Author

Jouret G, Egloff M, Landais E, Tassy O, Giuliano F, Karmous-Benailly H, Coutton C, Satre V, Devillard F, Dieterich K, Vieville G, Kuentz P, le Caignec C, Beneteau C, Isidor B, Nizon M, Callier P, Marquet V, Bieth E, Lévy J, Tabet AC, Lyonnet S, Baujat G, Rio M, Cartault F, Scheidecker S, Gouronc A, Schalk A, Jacquin C, Spodenkiewicz M, Angélini C, Pennamen P, Rooryck C, Doco-Fenzy M, and Poirsier C

Subjects
Humans, Comparative Genomic Hybridization, Syndrome, Genetic Association Studies, Abnormalities, Multiple genetics, Microcephaly genetics
Abstract

A small but growing body of scientific literature is emerging about clinical findings in patients with 19p13.3 microdeletion or duplication. Recently, a proximal 19p13.3 microduplication syndrome was described, associated with growth delay, microcephaly, psychomotor delay and dysmorphic features. The aim of our study was to better characterize the syndrome associated with duplications in the proximal 19p13.3 region (prox 19p13.3 dup), and to propose a comprehensive analysis of the underlying genomic mechanism. We report the largest cohort of patients with prox 19p13.3 dup through a collaborative study. We collected 24 new patients with terminal or interstitial 19p13.3 duplication characterized by array-based Comparative Genomic Hybridization (aCGH). We performed mapping, phenotype-genotype correlations analysis, critical region delineation and explored three-dimensional chromatin interactions by analyzing Topologically Associating Domains (TADs). We define a new 377 kb critical region (CR 1) in chr19: 3,116,922-3,494,377, GRCh37, different from the previously described critical region (CR 2). The new 377 kb CR 1 includes a TAD boundary and two enhancers whose common target is PIAS4. We hypothesize that duplications of CR 1 are responsible for tridimensional structural abnormalities by TAD disruption and misregulation of genes essentials for the control of head circumference during development, by breaking down the interactions between enhancers and the corresponding targeted gene., (© 2022 Wiley Periodicals LLC.)

Published
2023
Full Text
View/download PDF

50. A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet-Biedl syndrome.

Author

Delvallée C, Nicaise S, Antin M, Leuvrey AS, Nourisson E, Leitch CC, Kellaris G, Stoetzel C, Geoffroy V, Scheidecker S, Keren B, Depienne C, Klar J, Dahl N, Deleuze JF, Génin E, Redon R, Demurger F, Devriendt K, Mathieu-Dramard M, Poitou-Bernert C, Odent S, Katsanis N, Mandel JL, Davis EE, Dollfus H, and Muller J

Subjects
Cohort Studies, Female, Founder Effect, Gene Frequency, Humans, Male, Mutagenesis, Insertional, Pedigree, Whole Genome Sequencing, Bardet-Biedl Syndrome genetics, Microtubule-Associated Proteins genetics, Retroelements
Abstract

Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinitis pigmentosa, obesity, polydactyly, cognitive impairment and renal failure. Pathogenic variants in 24 genes account for the molecular basis of >80% of cases. Toward saturated discovery of the mutational basis of the disorder, we carefully explored our cohorts and identified a hominid-specific SINE-R/VNTR/Alu type F (SVA-F) insertion in exon 13 of BBS1 in eight families. In six families, the repeat insertion was found in trans with c.1169 T > G, p.Met390Arg and in two families the insertion was found in addition to other recessive BBS loci. Whole genome sequencing, de novo assembly and SNP array analysis were performed to characterize the genomic event. This insertion is extremely rare in the general population (found in 8 alleles of 8 BBS cases but not in >10 800 control individuals from gnomAD-SV) and due to a founder effect. Its 2435 bp sequence contains hallmarks of LINE1 mediated retrotransposition. Functional studies with patient-derived cell lines confirmed that the BBS1 SVA-F is deleterious as evidenced by a significant depletion of both mRNA and protein levels. Such findings highlight the importance of dedicated bioinformatics pipelines to identify all types of variation., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results