Author: "Thevenon J." - Searchworks@Jio Institute Digital Library Search Results

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373 results on '"Thevenon J."'

51. Unexpected diagnosis of a SHH nonsense variant causing a variable phenotype ranging from familial coloboma and Intellectual disability to isolated microcephaly

Author: Bruel, A.‐L., primary, Thevenon, J., additional, Huet, F., additional, Jean‐Marcais, N., additional, Odent, S., additional, Dubourg, C., additional, Lehalle, D., additional, Tran Mau‐Them, F., additional, Philippe, C., additional, Moutton, S., additional, Houcinat, N., additional, Gay, S., additional, Guibaud, L., additional, Duffourd, Y., additional, Rivière, J.‐B., additional, Faivre, L., additional, and Thauvin‐Robinet, C., additional more...
Published: 2018
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52. Caractérisation clinique et génétique d’une nouvelle dysplasie ectodermique en mosaïque

Author: Vabres, P., primary, Sorlin, A., additional, Kholmanskikh, S.S., additional, Demeer, B., additional, St-Onge, J., additional, Duffourd, Y., additional, Kuentz, P., additional, Courcet, J.-B., additional, Carmignac, V., additional, Bessis, D., additional, Boute, O., additional, Bron, A., additional, Captier, G., additional, Carmi, E., additional, Devauchelle, B., additional, Geneviève, D., additional, Gondry, C., additional, Guibaud, L., additional, Lafon, A., additional, Thevenon, J., additional, Bernard, G., additional, Dobyns, W.B., additional, Faivre, L., additional, Ross, M.E., additional, and Rivière, J.-B., additional more...
Published: 2017
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53. Quel profil des patients métastatiques hormonosensibles en 2016 ? Enquête descriptive de la pratique et de la prise en charge en France

Author: De la Taille, A., primary, Thevenon, J., additional, Bolla, M., additional, and Massard, C., additional
Published: 2017
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54. Measuring The Intensity Of Care Coordination For Blood Cancer Patients In France

Author: Mercier, G, primary, Duflos, C, additional, Kanouni, T, additional, Chevalier, J, additional, Thevenon, J, additional, and Cartron, G, additional
Published: 2017
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55. Using Observational Data From Registry In Cost-Effectiveness Evaluation of Metastatic Castration Resistant Prostate Cancer In France

Author: Leleu, H, primary, Wapenaar, R, additional, Klumper, E, additional, Capone, C, additional, de Beaucoudrey, L, additional, Thevenon, J, additional, and Chevalier, J, additional
Published: 2017
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56. Syndrome MIRAGE : données cliniques et biologiques chez 8 patients mutés pour le gène SAMD9

Author: Roucher-Boulez, F., primary, Mallet-Motak, D., additional, Kariyawasam, D., additional, Pinto, G., additional, Gerard, M., additional, Ribault, V., additional, Chalouhi, C., additional, Thevenon, J., additional, Brauner, R., additional, Bretones, P., additional, Jouk, P.S., additional, Tardy-Guidollet, V., additional, Signor, C. Ben, additional, and Morel, Y., additional more...
Published: 2017
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57. Expanding the clinical spectrum of recessive truncating mutations of KLHL7 to a Bohring-Opitz-like phenotype

Author: Bruel, Ange-Line, Bigoni, S., Kennedy, Joanna, Whiteford, M.L., Buxton, Chris, Parmeggiani, Giulia, Bon, B.W. van, Brunner, H.G., Hoischen, A., Thauvin-Robinet, Christel, Thevenon, J., Bruel, Ange-Line, Bigoni, S., Kennedy, Joanna, Whiteford, M.L., Buxton, Chris, Parmeggiani, Giulia, Bon, B.W. van, Brunner, H.G., Hoischen, A., Thauvin-Robinet, Christel, and Thevenon, J. more...
Abstract: Contains fulltext : 180428.pdf (publisher's version ) (Closed access)
Published: 2017

58. Fifteen years of research on oral-facial-digital syndromes: from 1 to 16 causal genes

Author: Bruel, A.L., Franco, B., Duffourd, Y., Thevenon, J., Jego, L., Lopez, E., Deleuze, J.F., Doummar, D., Giles, R.H., Johnson, C.A., Huynen, M.A., Chevrier, V., Burglen, L., Morleo, M., Desguerres, I., Pierquin, G., Doray, B., Gilbert-Dussardier, B., Reversade, B., Steichen-Gersdorf, E., Baumann, C., Panigrahi, I., Fargeot-Espaliat, A., Dieux, A., David, A., Goldenberg, A., Bongers, E.M., Gaillard, D., Argente, J., Aral, B., Gigot, N., St-Onge, J., Birnbaum, D., Phadke, S.R., Cormier-Daire, V., Eguether, T., Pazour, G.J., Herranz-Perez, V., Goldstein, J.S., Pasquier, L., Loget, P., Saunier, S., Megarbane, A., Rosnet, O., Leroux, M.R., Wallingford, J.B., Blacque, O.E., Nachury, M.V., Attie-Bitach, T., Riviere, J.B., Faivre, L., Thauvin-Robinet, C., Bruel, A.L., Franco, B., Duffourd, Y., Thevenon, J., Jego, L., Lopez, E., Deleuze, J.F., Doummar, D., Giles, R.H., Johnson, C.A., Huynen, M.A., Chevrier, V., Burglen, L., Morleo, M., Desguerres, I., Pierquin, G., Doray, B., Gilbert-Dussardier, B., Reversade, B., Steichen-Gersdorf, E., Baumann, C., Panigrahi, I., Fargeot-Espaliat, A., Dieux, A., David, A., Goldenberg, A., Bongers, E.M., Gaillard, D., Argente, J., Aral, B., Gigot, N., St-Onge, J., Birnbaum, D., Phadke, S.R., Cormier-Daire, V., Eguether, T., Pazour, G.J., Herranz-Perez, V., Goldstein, J.S., Pasquier, L., Loget, P., Saunier, S., Megarbane, A., Rosnet, O., Leroux, M.R., Wallingford, J.B., Blacque, O.E., Nachury, M.V., Attie-Bitach, T., Riviere, J.B., Faivre, L., and Thauvin-Robinet, C. more...
Abstract: Item does not contain fulltext, Oral-facial-digital syndromes (OFDS) gather rare genetic disorders characterised by facial, oral and digital abnormalities associated with a wide range of additional features (polycystic kidney disease, cerebral malformations and several others) to delineate a growing list of OFDS subtypes. The most frequent, OFD type I, is caused by a heterozygous mutation in the OFD1 gene encoding a centrosomal protein. The wide clinical heterogeneity of OFDS suggests the involvement of other ciliary genes. For 15 years, we have aimed to identify the molecular bases of OFDS. This effort has been greatly helped by the recent development of whole-exome sequencing (WES). Here, we present all our published and unpublished results for WES in 24 cases with OFDS. We identified causal variants in five new genes (C2CD3, TMEM107, INTU, KIAA0753 and IFT57) and related the clinical spectrum of four genes in other ciliopathies (C5orf42, TMEM138, TMEM231 and WDPCP) to OFDS. Mutations were also detected in two genes previously implicated in OFDS. Functional studies revealed the involvement of centriole elongation, transition zone and intraflagellar transport defects in OFDS, thus characterising three ciliary protein modules: the complex KIAA0753-FOPNL-OFD1, a regulator of centriole elongation; the Meckel-Gruber syndrome module, a major component of the transition zone; and the CPLANE complex necessary for IFT-A assembly. OFDS now appear to be a distinct subgroup of ciliopathies with wide heterogeneity, which makes the initial classification obsolete. A clinical classification restricted to the three frequent/well-delineated subtypes could be proposed, and for patients who do not fit one of these three main subtypes, a further classification could be based on the genotype. more...
Published: 2017

59. STAG1 mutations cause a novel cohesinopathy characterised by unspecific syndromic intellectual disability

Author: Lehalle, D., Mosca-Boidron, A.L., Begtrup, A., Boute-Benejean, O., Charles, P., Cho, M.T., Clarkson, A., Devinsky, O., Duffourd, Y., Duplomb-Jego, L., Gerard, B., Jacquette, A., Kuentz, P., Masurel-Paulet, A., McDougall, C., Moutton, S., Olivie, H., Park, S.M., Rauch, A., Revencu, N., Riviere, J.B., Rubin, K., Simonic, I., Shears, D.J., Smol, T., Tavares, A.L.T., Terhal, P., Thevenon, J., Gassen, K. van, Vincent-Delorme, C., Willemsen, M.H., Wilson, G.N., Zackai, E., Zweier, C., Callier, P., Thauvin-Robinet, C., Faivre, L., Lehalle, D., Mosca-Boidron, A.L., Begtrup, A., Boute-Benejean, O., Charles, P., Cho, M.T., Clarkson, A., Devinsky, O., Duffourd, Y., Duplomb-Jego, L., Gerard, B., Jacquette, A., Kuentz, P., Masurel-Paulet, A., McDougall, C., Moutton, S., Olivie, H., Park, S.M., Rauch, A., Revencu, N., Riviere, J.B., Rubin, K., Simonic, I., Shears, D.J., Smol, T., Tavares, A.L.T., Terhal, P., Thevenon, J., Gassen, K. van, Vincent-Delorme, C., Willemsen, M.H., Wilson, G.N., Zackai, E., Zweier, C., Callier, P., Thauvin-Robinet, C., and Faivre, L. more...
Abstract: Item does not contain fulltext, BACKGROUND: Cohesinopathies are rare neurodevelopmental disorders arising from a dysfunction in the cohesin pathway, which enables chromosome segregation and regulates gene transcription. So far, eight genes from this pathway have been reported in human disease. STAG1 belongs to the STAG subunit of the core cohesin complex, along with five other subunits. This work aimed to identify the phenotype ascribed to STAG1 mutations. METHODS: Among patients referred for intellectual disability (ID) in genetics departments worldwide, array-comparative genomic hybridisation (CGH), gene panel, whole-exome sequencing or whole-genome sequencing were performed following the local diagnostic standards. RESULTS: A mutation in STAG1 was identified in 17 individuals from 16 families, 9 males and 8 females aged 2-33 years. Four individuals harboured a small microdeletion encompassing STAG1; three individuals from two families had an intragenic STAG1 deletion. Six deletions were identified by array-CGH, one by whole-exome sequencing. Whole-exome sequencing found de novo heterozygous missense or frameshift STAG1 variants in eight patients, a panel of genes involved in ID identified a missense and a frameshift variant in two individuals. The 17 patients shared common facial features, with wide mouth and deep-set eyes. Four individuals had mild microcephaly, seven had epilepsy. CONCLUSIONS: We report an international series of 17 individuals from 16 families presenting with syndromic unspecific ID that could be attributed to a STAG1 deletion or point mutation. This first series reporting the phenotype ascribed to mutation in STAG1 highlights the importance of data sharing in the field of rare disorders. more...
Published: 2017

60. Stress-tests EBA-BCE 2014 – Comparaisons internationales

Author: Camara B., Castellani F.-D., Devost G., Heam J.-C., Kaminski A.-L., Labonne C., Martin V., and Thevenon J.-L.
Abstract: Les tests de résistance, conduits par l’Autorité bancaire européenne (EBA) et la Banque centrale européenne (BCE) en 2014, se sont inscrits dans le cadre plus large de l’exercice d’évaluation complète des bilans des 130 plus grandes banques de la zone euro menée par la BCE et les autorités nationales (« comprehensive assessment »). À l’image des précédents exercices européens menés sous l’égide de l’EBA, les stress tests 2014 ont été réalisés selon une approche dite « bottom-up ». La capacité de résistance des établissements en termes de solvabilité a été évaluée à partir de deux scénarios hypothétiques de 3 ans (un scénario central, un scénario stressé), dont les banques devaient mesurer les impacts sur leur situation, en appliquant une méthodologie commune. L’appréciation de leur résistance s’effectuait par comparaison des résultats avec des ratios de référence, respectivement un ratio CET1 minimum de 8% et de 5,5%, devant être respectés tout au long de la période considérée. En termes de sévérité, le scénario stressé EBA-BCE 2014 ressort comme plus conservateur que celui de l’exercice EBA de 2011 et comparable aux scénarios stressés appliqués par la Fed dans son dernier exercice de stress test (CCAR 2014). Les chocs appliqués aux différents pays participants ne sont pas de même sévérité : par exemple, le choc appliqué à l’économie française est légèrement plus sévère que le choc appliqué à l’économie espagnole mais moins que les scénarios retenus pour le Royaume-Uni et l’Allemagne, plus ouverte sur l’extérieur. Le secteur bancaire français se caractérise par un niveau de capitalisation élevé au point de départ (fin décembre 2013) et au terme de l’exercice de stress (fin 2016). Fin 2013 et après prise en compte de l’impact de la revue de la qualité des actifs, le ratio CET1 agrégé des banques françaises, calculé selon le dispositif réglementaire CRD4/CRR et sur le périmètre couvert par la BCE, s’élève à 11,3%, et ressort à 9,0% en 2016 dans le cadre du scénario stressé, soit une érosion du ratio de solvabilité de 230 bp environ. En termes d’écart au compte central, le ratio CET1 2016 résultant du scénario stressé est de 281 bp inférieur au ratio CET1 2016 du scénario central. Au final en 2016, la capitalisation du secteur bancaire français atteint ainsi un niveau supérieur à la moyenne européenne (8,4%). Le ratio CET1 agrégé sur le périmètre couvert par l’EBA évolue sous l’effet des facteurs suivants : • Le volet crédit est l’un des facteurs qui affectent le plus le ratio de solvabilité dans le cadre du stress test. La sévérité relative du stress, mesurée par l’écart de ratio CET1 moyen en 2016 entre le compte central et le scénario stressé après application du seul stress de crédit (hors titrisation), place la France parmi les pays les moins affectés (-135bp, contre -181bp pour l’UE). Ces résultats recouvrent néanmoins des situations très différentes selon les pays et les banques considérés, compte tenu de la diversité des facteurs sous-tendant l’évolution du CET1. Si l’on distingue par grandes catégories de portefeuilles, il apparaît que le stress appliqué par les banques françaises est, en termes de sévérité, dans la moyenne européenne en matière d’immobilier résidentiel, et dans la fourchette basse pour le crédit aux entreprises. La conclusion détaille l’essentiel des mesures de supervision spécifiques prévues pour les institutions systémiques des secteurs de la banque et de l’assurance. • Le volet « marge d’intérêts » du stress test – combinaison de l’effet de l’évolution des taux d’intérêt et de l’évolution du coût de financement des banques – est également l’un des facteurs qui pèsent le plus dans l’évolution de ratio de solvabilité du stress test. En agrégé pour les banques françaises, ce volet contribue pour 60 bp au total de l’écart (281 bp) ratio CET1 2016 dans les deux scénarios. Avec une perte de 15,6% de marge nette d’intérêts en moyenne sur 3 ans par rapport à l’année 2013, les banques françaises apparaissent parmi les plus touchées par ce volet du stress test. • En matière de risque souverain, le scénario stressé était a priori particulièrement pénalisant pour la France. Pour autant, l’effet du stress souverain sur les banques françaises est relativement modéré, tant sur le portefeuille bancaire que sur le portefeuille de marché : ces résultats s’expliquent entre autres par le fait que les banques françaises sont majoritairement exposées sur leur souverain domestique, jugé peu risqué. • Enfin, s’agissant du volet marché, la France occupe une position médiane avec une dégradation de 21bp au titre des revenus et 20bp au titre des risques pondérés more...
Published: 2015

61. Further delineation of a rare recessive encephalomyopathy linked to mutations in GFER thanks to data sharing of whole exome sequencing data

Author: Nambot, S., primary, Gavrilov, D., additional, Thevenon, J., additional, Bruel, A.L., additional, Bainbridge, M., additional, Rio, M., additional, Goizet, C., additional, Rötig, A., additional, Jaeken, J., additional, Niu, N., additional, Xia, F., additional, Vital, A., additional, Houcinat, N., additional, Mochel, F., additional, Kuentz, P., additional, Lehalle, D., additional, Duffourd, Y., additional, Rivière, J.B., additional, Thauvin‐Robinet, C., additional, Beaudet, A.L., additional, and Faivre, L., additional more...
Published: 2017
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62. Autosomal recessive variations of TBX6 , from congenital scoliosis to spondylocostal dysostosis

Author: Lefebvre, M., primary, Duffourd, Y., additional, Jouan, T., additional, Poe, C., additional, Jean-Marçais, N., additional, Verloes, A., additional, St-Onge, J., additional, Riviere, J.-B., additional, Petit, F., additional, Pierquin, G., additional, Demeer, B., additional, Callier, P., additional, Thauvin-Robinet, C., additional, Faivre, L., additional, and Thevenon, J., additional more...
Published: 2017
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63. Xq28 duplication includingMECP2in six unreported affected females: what can we learn for diagnosis and genetic counselling?

Author: El Chehadeh, S., primary, Touraine, R., additional, Prieur, F., additional, Reardon, W., additional, Bienvenu, T., additional, Chantot-Bastaraud, S., additional, Doco-Fenzy, M., additional, Landais, E., additional, Philippe, C., additional, Marle, N., additional, Callier, P., additional, Mosca-Boidron, A.-L., additional, Mugneret, F., additional, Le Meur, N., additional, Goldenberg, A., additional, Guerrot, A.-M., additional, Chambon, P., additional, Satre, V., additional, Coutton, C., additional, Jouk, P.-S., additional, Devillard, F., additional, Dieterich, K., additional, Afenjar, A., additional, Burglen, L., additional, Moutard, M.-L., additional, Addor, M.-C., additional, Lebon, S., additional, Martinet, D., additional, Alessandri, J.-L., additional, Doray, B., additional, Miguet, M., additional, Devys, D., additional, Saugier-Veber, P., additional, Drunat, S., additional, Aral, B., additional, Kremer, V., additional, Rondeau, S., additional, Tabet, A.-C., additional, Thevenon, J., additional, Thauvin-Robinet, C., additional, Perreton, N., additional, Des Portes, V., additional, and Faivre, L., additional more...
Published: 2017
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64. Disruption of POGZ Is Associated with Intellectual Disability and Autism Spectrum Disorders

Author: Stessman, H.A., Willemsen, M.H., Fenckova, M., Penn, O., Hoischen, A., Xiong, B., Wang, T., Hoekzema, K., Vives, L., Vogel, I., Brunner, H.G., Burgt, I. van der, Ockeloen, C.W., Schuurs-Hoeijmakers, J.H.M., Wassink-Ruiter, J.S., Stumpel, C., Stevens, S.J., Vles, H.S., Marcelis, C.M., Bokhoven, H. van, Cantagrel, V., Colleaux, L., Nicouleau, M., Lyonnet, S., Bernier, R.A., Gerdts, J., Coe, B.P., Romano, C, Alberti, A., Grillo, L., Scuderi, C., Nordenskjold, M., Kvarnung, M., Guo, H., Xia, K., Piton, A., Gerard, B., Genevieve, D., Delobel, B., Lehalle, D., Perrin, L., Prieur, F., Thevenon, J., Gecz, J., Shaw, M., Pfundt, R., Keren, B., Jacquette, A., Schenck, A., Eichler, E.E., Kleefstra, T., Stessman, H.A., Willemsen, M.H., Fenckova, M., Penn, O., Hoischen, A., Xiong, B., Wang, T., Hoekzema, K., Vives, L., Vogel, I., Brunner, H.G., Burgt, I. van der, Ockeloen, C.W., Schuurs-Hoeijmakers, J.H.M., Wassink-Ruiter, J.S., Stumpel, C., Stevens, S.J., Vles, H.S., Marcelis, C.M., Bokhoven, H. van, Cantagrel, V., Colleaux, L., Nicouleau, M., Lyonnet, S., Bernier, R.A., Gerdts, J., Coe, B.P., Romano, C, Alberti, A., Grillo, L., Scuderi, C., Nordenskjold, M., Kvarnung, M., Guo, H., Xia, K., Piton, A., Gerard, B., Genevieve, D., Delobel, B., Lehalle, D., Perrin, L., Prieur, F., Thevenon, J., Gecz, J., Shaw, M., Pfundt, R., Keren, B., Jacquette, A., Schenck, A., Eichler, E.E., and Kleefstra, T. more...
Abstract: Item does not contain fulltext, Intellectual disability (ID) and autism spectrum disorders (ASD) are genetically heterogeneous, and a significant number of genes have been associated with both conditions. A few mutations in POGZ have been reported in recent exome studies; however, these studies do not provide detailed clinical information. We collected the clinical and molecular data of 25 individuals with disruptive mutations in POGZ by diagnostic whole-exome, whole-genome, or targeted sequencing of 5,223 individuals with neurodevelopmental disorders (ID primarily) or by targeted resequencing of this locus in 12,041 individuals with ASD and/or ID. The rarity of disruptive mutations among unaffected individuals (2/49,401) highlights the significance (p = 4.19 x 10(-13); odds ratio = 35.8) and penetrance (65.9%) of this genetic subtype with respect to ASD and ID. By studying the entire cohort, we defined common phenotypic features of POGZ individuals, including variable levels of developmental delay (DD) and more severe speech and language delay in comparison to the severity of motor delay and coordination issues. We also identified significant associations with vision problems, microcephaly, hyperactivity, a tendency to obesity, and feeding difficulties. Some features might be explained by the high expression of POGZ, particularly in the cerebellum and pituitary, early in fetal brain development. We conducted parallel studies in Drosophila by inducing conditional knockdown of the POGZ ortholog row, further confirming that dosage of POGZ, specifically in neurons, is essential for normal learning in a habituation paradigm. Combined, the data underscore the pathogenicity of loss-of-function mutations in POGZ and define a POGZ-related phenotype enriched in specific features. more...
Published: 2016

65. BCL11A Haploinsufficiency Causes an Intellectual Disability Syndrome and Dysregulates Transcription

Author: Dias, C., Estruch, S.B., Graham, S.A., McRae, J., Sawiak, S.J., Hurst, J.A., Joss, S.K., Holder, S.E., Morton, J.E., Turner, C., Thevenon, J., Mellul, K., Sanchez-Andrade, G., Ibarra-Soria, X., Deriziotis, P., Santos, R.F., Lee, S.C., Faivre, L., Kleefstra, T., Liu, P., Hurles, M.E., Fisher, S.E., Logan, D.W., Dias, C., Estruch, S.B., Graham, S.A., McRae, J., Sawiak, S.J., Hurst, J.A., Joss, S.K., Holder, S.E., Morton, J.E., Turner, C., Thevenon, J., Mellul, K., Sanchez-Andrade, G., Ibarra-Soria, X., Deriziotis, P., Santos, R.F., Lee, S.C., Faivre, L., Kleefstra, T., Liu, P., Hurles, M.E., Fisher, S.E., and Logan, D.W. more...
Abstract: Contains fulltext : 167380.pdf (publisher's version ) (Open Access), Intellectual disability (ID) is a common condition with considerable genetic heterogeneity. Next-generation sequencing of large cohorts has identified an increasing number of genes implicated in ID, but their roles in neurodevelopment remain largely unexplored. Here we report an ID syndrome caused by de novo heterozygous missense, nonsense, and frameshift mutations in BCL11A, encoding a transcription factor that is a putative member of the BAF swi/snf chromatin-remodeling complex. Using a comprehensive integrated approach to ID disease modeling, involving human cellular analyses coupled to mouse behavioral, neuroanatomical, and molecular phenotyping, we provide multiple lines of functional evidence for phenotypic effects. The etiological missense variants cluster in the amino-terminal region of human BCL11A, and we demonstrate that they all disrupt its localization, dimerization, and transcriptional regulatory activity, consistent with a loss of function. We show that Bcl11a haploinsufficiency in mice causes impaired cognition, abnormal social behavior, and microcephaly in accordance with the human phenotype. Furthermore, we identify shared aberrant transcriptional profiles in the cortex and hippocampus of these mouse models. Thus, our work implicates BCL11A haploinsufficiency in neurodevelopmental disorders and defines additional targets regulated by this gene, with broad relevance for our understanding of ID and related syndromes. more...
Published: 2016

66. Clinical and molecular findings in 39 patients with KBG syndrome caused by deletion or mutation of ANKRD11

Author: Goldenberg, A., Riccardi, F., Tessier, A., Pfundt, R.P., Busa, T., Cacciagli, P., Capri, Y., Coutton, C., Delahaye-Duriez, A., Frebourg, T., Gatinois, V., Guerrot, A.M., Genevieve, D., Lecoquierre, F., Jacquette, A., Kien, P. Khau Van, Leheup, B., Marlin, S., Verloes, A., Michaud, V., Nadeau, G., Mignot, C., Parent, P., Rossi, M., Toutain, A., Schaefer, E., Thauvin-Robinet, C., Maldergem, L. Van, Thevenon, J., Satre, V., Perrin, L., Vincent-Delorme, C., Sorlin, A., Missirian, C., Villard, L., Mancini, J., Saugier-Veber, P., Philip, N., Goldenberg, A., Riccardi, F., Tessier, A., Pfundt, R.P., Busa, T., Cacciagli, P., Capri, Y., Coutton, C., Delahaye-Duriez, A., Frebourg, T., Gatinois, V., Guerrot, A.M., Genevieve, D., Lecoquierre, F., Jacquette, A., Kien, P. Khau Van, Leheup, B., Marlin, S., Verloes, A., Michaud, V., Nadeau, G., Mignot, C., Parent, P., Rossi, M., Toutain, A., Schaefer, E., Thauvin-Robinet, C., Maldergem, L. Van, Thevenon, J., Satre, V., Perrin, L., Vincent-Delorme, C., Sorlin, A., Missirian, C., Villard, L., Mancini, J., Saugier-Veber, P., and Philip, N. more...
Abstract: Item does not contain fulltext, KBG syndrome, due to ANKRD11 alteration is characterized by developmental delay, short stature, dysmorphic facial features, and skeletal anomalies. We report a clinical and molecular study of 39 patients affected by KBG syndrome. Among them, 19 were diagnosed after the detection of a 16q24.3 deletion encompassing the ANKRD11 gene by array CGH. In the 20 remaining patients, the clinical suspicion was confirmed by the identification of an ANKRD11 mutation by direct sequencing. We present arguments to modulate the previously reported diagnostic criteria. Macrodontia should no longer be considered a mandatory feature. KBG syndrome is compatible with autonomous life in adulthood. Autism is less frequent than previously reported. We also describe new clinical findings with a potential impact on the follow-up of patients, such as precocious puberty and a case of malignancy. Most deletions remove the 5'end or the entire coding region but never extend toward 16q telomere suggesting that distal 16q deletion could be lethal. Although ANKRD11 appears to be a major gene associated with intellectual disability, KBG syndrome remains under-diagnosed. NGS-based approaches for sequencing will improve the detection of point mutations in this gene. Broad knowledge of the clinical phenotype is essential for a correct interpretation of the molecular results. (c) 2016 Wiley Periodicals, Inc. more...
Published: 2016

67. Dominant variants in the splicing factor PUF60 cause a recognizable syndrome with intellectual disability, heart defects and short stature

Author: Chehadeh, S. El, Kerstjens-Frederikse, W.S., Thevenon, J., Kuentz, P., Bruel, A.L., Thauvin-Robinet, C., Bensignor, C., Dollfus, H., Laugel, V., Riviere, J.B., Duffourd, Y., Bonnet, C., Robert, M.P., Isaiko, R., Straub, M., Creuzot-Garcher, C., Calvas, P., Chassaing, N., Loeys, B., Reyniers, E., Vandeweyer, G., Kooy, F., Hancarova, M., Havlovicova, M., Prchalova, D., Sedlacek, Z., Gilissen, C.F., Pfundt, R.P., Wassink-Ruiter, J.S., Faivre, L., Chehadeh, S. El, Kerstjens-Frederikse, W.S., Thevenon, J., Kuentz, P., Bruel, A.L., Thauvin-Robinet, C., Bensignor, C., Dollfus, H., Laugel, V., Riviere, J.B., Duffourd, Y., Bonnet, C., Robert, M.P., Isaiko, R., Straub, M., Creuzot-Garcher, C., Calvas, P., Chassaing, N., Loeys, B., Reyniers, E., Vandeweyer, G., Kooy, F., Hancarova, M., Havlovicova, M., Prchalova, D., Sedlacek, Z., Gilissen, C.F., Pfundt, R.P., Wassink-Ruiter, J.S., and Faivre, L. more...
Abstract: Item does not contain fulltext, Verheij syndrome, also called 8q24.3 microdeletion syndrome, is a rare condition characterized by ante- and postnatal growth retardation, microcephaly, vertebral anomalies, joint laxity/dislocation, developmental delay (DD), cardiac and renal defects and dysmorphic features. Recently, PUF60 (Poly-U Binding Splicing Factor 60 kDa), which encodes a component of the spliceosome, has been discussed as the best candidate gene for the Verheij syndrome phenotype, regarding the cardiac and short stature phenotype. To date, only one patient has been reported with a de novo variant in PUF60 that probably affects function (c.505C>T leading to p.(His169Tyr)) associated with DD, microcephaly, craniofacial and cardiac defects. Additional patients were required to confirm the pathogenesis of this association and further delineate the clinical spectrum. Here we report five patients with de novo heterozygous variants in PUF60 identified using whole exome sequencing. Variants included a splice-site variant (c.24+1G>C), a frameshift variant (p.(Ile136Thrfs*31)), two nonsense variants (p.(Arg448*) and p.(Lys301*)) and a missense change (p.(Val483Ala)). All six patients with a PUF60 variant (the five patients of the present study and the unique reported patient) have the same core facial gestalt as 8q24.3 microdeletions patients, associated with DD. Other findings include feeding difficulties (3/6), cardiac defects (5/6), short stature (5/6), joint laxity and/or dislocation (5/6), vertebral anomalies (3/6), bilateral microphthalmia and irido-retinal coloboma (1/6), bilateral optic nerve hypoplasia (2/6), renal anomalies (2/6) and branchial arch defects (2/6). These results confirm that PUF60 is a major driver for the developmental, craniofacial, skeletal and cardiac phenotypes associated with the 8q24.3 microdeletion. more...
Published: 2016

68. OFIP/KIAA0753 forms a complex with OFD1 and FOR20 at pericentriolar satellites and centrosomes and is mutated in one individual with oral-facial-digital syndrome

Author: Chevrier, V., Bruel, A.L., Dam, T.J. van, Franco, B., Scalzo, M. Lo, Lembo, F., Audebert, S., Baudelet, E., Isnardon, D., Bole, A., Borg, J.P., Kuentz, P., Thevenon, J., Burglen, L., Faivre, L., Riviere, J.B., Huynen, M.A., Birnbaum, D., Rosnet, O., Thauvin-Robinet, C., Chevrier, V., Bruel, A.L., Dam, T.J. van, Franco, B., Scalzo, M. Lo, Lembo, F., Audebert, S., Baudelet, E., Isnardon, D., Bole, A., Borg, J.P., Kuentz, P., Thevenon, J., Burglen, L., Faivre, L., Riviere, J.B., Huynen, M.A., Birnbaum, D., Rosnet, O., and Thauvin-Robinet, C. more...
Abstract: Item does not contain fulltext, Oral-facial-digital (OFD) syndromes are rare heterogeneous disorders characterized by the association of abnormalities of the face, the oral cavity and the extremities, some due to mutations in proteins of the transition zone of the primary cilia or the closely associated distal end of centrioles. These two structures are essential for the formation of functional cilia, and for signaling events during development. We report here causal compound heterozygous mutations of KIAA0753/OFIP in a patient with an OFD VI syndrome. We show that the KIAA0753/OFIP protein, whose sequence is conserved in ciliated species, associates with centrosome/centriole and pericentriolar satellites in human cells and forms a complex with FOR20 and OFD1. The decreased expression of any component of this ternary complex in RPE1 cells causes a defective recruitment onto centrosomes and satellites. The OFD KIAA0753/OFIP mutant loses its capacity to interact with FOR20 and OFD1, which may be the molecular basis of the defect. We also show that KIAA0753/OFIP has microtubule-stabilizing activity. OFD1 and FOR20 are known to regulate the integrity of the centriole distal end, confirming that this structural element is a target of importance for pathogenic mutations in ciliopathies. more...
Published: 2016

69. Expanding the Phenotype Associated with NAA10-Related N-Terminal Acetylation Deficiency

Author: Saunier, C. (Chloé), Støve, S.I. (Svein Isungset), Popp, B. (Bernt), Gérard, B. (Bénédicte), Blenski, M. (Marina), Ahmew, N. (Nicholas), de Bie, C. (Charlotte), Goldenberg, P. (Paula), Isidor, B. (Bertrand), Keren, B. (Boris), Leheup, B. (Bruno), Lampert, L. (Laetitia), Mignot, A., Tezcan, K. (Kamer), Mancini, G.M.S. (Grazia), Nava, C. (Caroline), Wasserstein, M. (Melissa), Bruel, A.-L. (Ange-Line), Thevenon, J. (Julien), Masurel, A. (Alice), Duffourd, Y. (Yannis), Kuentz, P. (Paul), Huet, F. (Frédéric), Riviere, J.-B., Slegtenhorst, M.A. (Marjon) van, Faivre, L. (Laurence), Piton, A. (Amélie), Reis, A. (André), Arnesen, T. (Thomas), Thauvin-Robinet, C. (Christel), Zweier, C. (Christiane), Saunier, C. (Chloé), Støve, S.I. (Svein Isungset), Popp, B. (Bernt), Gérard, B. (Bénédicte), Blenski, M. (Marina), Ahmew, N. (Nicholas), de Bie, C. (Charlotte), Goldenberg, P. (Paula), Isidor, B. (Bertrand), Keren, B. (Boris), Leheup, B. (Bruno), Lampert, L. (Laetitia), Mignot, A., Tezcan, K. (Kamer), Mancini, G.M.S. (Grazia), Nava, C. (Caroline), Wasserstein, M. (Melissa), Bruel, A.-L. (Ange-Line), Thevenon, J. (Julien), Masurel, A. (Alice), Duffourd, Y. (Yannis), Kuentz, P. (Paul), Huet, F. (Frédéric), Riviere, J.-B., Slegtenhorst, M.A. (Marjon) van, Faivre, L. (Laurence), Piton, A. (Amélie), Reis, A. (André), Arnesen, T. (Thomas), Thauvin-Robinet, C. (Christel), and Zweier, C. (Christiane) more...
Abstract: N-terminal acetylation is a common protein modification in eukaryotes associated with numerous cellular processes. Inherited mutations in NAA10, encoding the catalytic subunit of the major N-terminal acetylation complex NatA have been associated with diverse, syndromic X-linked recessive disorders, whereas de novo missense mutations have been reported in one male and one female individual with severe intellectual disability but otherwise unspecific phenotypes. Thus, the full genetic and clinical spectrum of NAA10 deficiency is yet to be delineated. We identified three different novel and one known missense mutation in NAA10, de novo in 11 females, and due to maternal germ line mosaicism in another girl and her more severely affected and deceased brother. In vitro enzymatic assays for the novel, recurrent mutations p.(Arg83Cys) and p.(Phe128Leu) revealed reduced catalytic activity. X-inactivation was random in five females. The core phenotype of X-linked NAA10-related N-terminal-acetyltransferase deficiency in both males and females includes developmental delay, severe intellectual disability, postnatal growth failure with severe microcephaly, and skeletal or cardiac anomalies. Genotype-phenotype correlations within and between both genders are complex and may include various factors such as location and nature of mutations, enzymatic stability and activity, and X-inactivation in females. more...
Published: 2016
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70. Expanding the Phenotype Associated with NAA10-Related N-Terminal Acetylation Deficiency

Author: Saunier, C, Stove, S I, Popp, B, Gerard, B, Blenski, M, AhMew, N, de Bie, C, Goldenberg, P, Isidor, B, Keren, B, Leheup, B, Lampert, L, Mignot, C, Tezcan, K, Verheijen - Mancini, Grazia, Nava, C, Wasserstein, M, Bruel, A L, Thevenon, J, Masurel, A, Duffourd, Y, Kuentz, P, Huet, F, Riviere, JB, van Slegtenhorst, Marjon, Faivre, L, Piton, A, Reis, A, Arnesen, T, Thauvin-Robinet, C, Zweier, C, Saunier, C, Stove, S I, Popp, B, Gerard, B, Blenski, M, AhMew, N, de Bie, C, Goldenberg, P, Isidor, B, Keren, B, Leheup, B, Lampert, L, Mignot, C, Tezcan, K, Verheijen - Mancini, Grazia, Nava, C, Wasserstein, M, Bruel, A L, Thevenon, J, Masurel, A, Duffourd, Y, Kuentz, P, Huet, F, Riviere, JB, van Slegtenhorst, Marjon, Faivre, L, Piton, A, Reis, A, Arnesen, T, Thauvin-Robinet, C, and Zweier, C more...
Published: 2016

71. Mutation en mosaïque de KITLG dans l’hypermélanose nævoïde

Author: Sorlin, A., primary, Maruani, A., additional, Kuentz, P., additional, Duffourd, Y., additional, St-Onge, J., additional, Chevarin, M., additional, Jouan, T., additional, Aubriot-Lorton, M.-H., additional, Thauvin-Robinet, C., additional, Thevenon, J., additional, Faivre, L., additional, Rivière, J.-B., additional, and Vabres, P., additional more...
Published: 2016
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72. Mosaic‐activating FGFR2 mutation in two fetuses with papillomatous pedunculated sebaceous naevus

Author: Kuentz, P., primary, Fraitag, S., additional, Gonzales, M., additional, Dhombres, F., additional, St‐Onge, J., additional, Duffourd, Y., additional, Joyé, N., additional, Jouannic, J.‐M., additional, Picard, A., additional, Marle, N., additional, Thevenon, J., additional, Thauvin‐Robinet, C., additional, Faivre, L., additional, Rivière, J.‐B., additional, and Vabres, P., additional more...
Published: 2016
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73. 151 Postzygotic KITLG mutation in a congenital non-progressive linear nevoid hyperpigmentation

Author: Sorlin, A., primary, Maruani, A., additional, Rivière, J., additional, Duffourd, Y., additional, Kuentz, P., additional, Jouan, T., additional, Thauvin-Robinet, C., additional, Thevenon, J., additional, Faivre, L., additional, and Vabres, P., additional more...
Published: 2016
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74. 186 Mutational spectrum in PIK3CA -Related Overgrowth Spectrum (PROS) and recommendations for molecular testing

Author: Kuentz, P., primary, Duffourd, Y., additional, St-Onge, J., additional, Jouan, T., additional, Sorlin, A., additional, Thauvin-Robinet, C., additional, Thevenon, J., additional, Rivière, J., additional, Faivre, L., additional, and Vabres, P., additional more...
Published: 2016
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75. Autosomal recessive truncating MAB21L1 mutation associated with a syndromic scrotal agenesis

Author: Bruel, A.‐L., primary, Masurel‐Paulet, A., additional, Rivière, J.‐B., additional, Duffourd, Y., additional, Lehalle, D., additional, Bensignor, C., additional, Huet, F., additional, Borgnon, J., additional, Roucher, F., additional, Kuentz, P., additional, Deleuze, J.‐F., additional, Thauvin‐Robinet, C., additional, Faivre, L., additional, and Thevenon, J., additional more...
Published: 2016
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76. Rett‐like phenotypes: expanding the genetic heterogeneity to theKCNA2gene and first familial case ofCDKL5‐related disease

Author: Allou, L., primary, Julia, S., additional, Amsallem, D., additional, El Chehadeh, S., additional, Lambert, L., additional, Thevenon, J., additional, Duffourd, Y., additional, Saunier, A., additional, Bouquet, P., additional, Pere, S., additional, Moustaïne, A., additional, Ruaud, L., additional, Roth, V., additional, Jonveaux, P., additional, and Philippe, C., additional more...
Published: 2016
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77. Autosomal recessive IFT57 hypomorphic mutation cause ciliary transport defect in unclassified oral–facial–digital syndrome with short stature and brachymesophalangia

Author: Thevenon, J., primary, Duplomb, L., additional, Phadke, S., additional, Eguether, T., additional, Saunier, A., additional, Avila, M., additional, Carmignac, V., additional, Bruel, A.‐L., additional, St‐Onge, J., additional, Duffourd, Y., additional, Pazour, G.J., additional, Franco, B., additional, Attie‐Bitach, T., additional, Masurel‐Paulet, A., additional, Rivière, J.‐B., additional, Cormier‐Daire, V., additional, Philippe, C., additional, Faivre, L., additional, and Thauvin‐Robinet, C., additional more...
Published: 2016
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78. 782 Detection of mosaic copy-number variation from whole-exome sequencing in mosaic cutaneous disorders using XHMM and custom SNP approach

Author: Sorlin, A., Tisserant, Thevenon, J., Carmignac, V., Duffourd, Y., Kuentz, P., Rivière, J., Thauvin-Robinet, C., Faivre, L., Callier, P., and Vabres, P.
Published: 2018
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79. Mosaicism due to postzygotic mutations in women with focal dermal hypoplasia.

Author: Heinz, L., Bourrat, E., Vabres, P., Thevenon, J., Hotz, A., Hörer, S., Küsel, J., Zimmer, A.D., Alter, S., Happle, R., and Fischer, J.
Subjects: GENETIC disorders
Abstract: Summary: Focal dermal hypoplasia (FDH, Goltz syndrome, MIM #305600) constitutes a rare multisystem genetic disorder of the skin, skeleton, teeth and eyes with considerable variation in the clinical features. FDH is transmitted as an X‐linked dominant trait and is caused by mutations in PORCN. In male children, hemizygous PORCN mutations are lethal in utero. Around 300 cases have been reported in the literature to date. About 10% of them are male patients presenting with either Klinefelter syndrome (karyotype 47, XXY) or mosaicism of a postzygotic mutation. Here we describe four cases of women with typical features of FDH, in whom a PORCN mutation was found in DNA from affected cutaneous tissue but not in DNA from peripheral blood. This study suggests that mosaicism caused by a postzygotic mutation occurs more often than assumed to date in female patients with FDH. A negative analysis performed on peripheral blood DNA does not exclude the diagnosis of FDH and it is therefore of practical importance to analyse DNA from the affected skin in order to identify low‐level mosaicism and thus to improve diagnostic precision. In total, we found two missense variants, one novel indel and one novel splice‐site variant. Individuals harbouring postzygotic mosaicism run a risk of transmitting the disorder to their daughters, because the maternal mosaic could also affect the gonads. What's already known about this topic? Mutations in PORCN cause focal dermal hypoplasia (FDH).In male children, hemizygous PORCN mutations are lethal in utero.To date, only around 300 patients with mutations in PORCN have been reported. What does this study add? In four women affected by FDH, PORCN mutations were found to be present in affected cutaneous tissue but not in peripheral blood.Negative mutation analysis of blood samples does not exclude the diagnosis of FDH, as a mosaic constellation due to postzygotic mutations has been repeatedly observed in female patients with FDH as shown in this study. Linked Comment:Traupe. Br J Dermatol 2019; 180:461–462. Plain language summary available online [ABSTRACT FROM AUTHOR] more...
Published: 2019
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80. CA-087: Qualité de vie liée à la santé orale des patients diabétiques de type 1

Author: Devoize, L., primary, Thevenon, J., additional, Batisse-Lignier, M., additional, Desbiez, F., additional, Roche, B., additional, and Tauveron, I., additional
Published: 2016
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81. Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity

Author: Rocker, N. de, Vergult, S., Koolen, D.A., Jacobs, E., Hoischen, A., Zeesman, S., Bang, B., Bena, F., Bockaert, N., Bongers, E.M.H.F., Ravel, T. de, Devriendt, K., Giglio, S., Faivre, L., Joss, S., Maas, S., Marle, N., Novara, F., Nowaczyk, M.J., Peeters, H., Polstra, A., Roelens, F., Rosenberg, C., Thevenon, J., Tumer, Z., Vanhauwaert, S., Varvagiannis, K., Willaert, A., Willemsen, M.H., Willems, M., Zuffardi, O., Coucke, P., Speleman, F., Eichler, E.E., Kleefstra, T., Menten, B., Rocker, N. de, Vergult, S., Koolen, D.A., Jacobs, E., Hoischen, A., Zeesman, S., Bang, B., Bena, F., Bockaert, N., Bongers, E.M.H.F., Ravel, T. de, Devriendt, K., Giglio, S., Faivre, L., Joss, S., Maas, S., Marle, N., Novara, F., Nowaczyk, M.J., Peeters, H., Polstra, A., Roelens, F., Rosenberg, C., Thevenon, J., Tumer, Z., Vanhauwaert, S., Varvagiannis, K., Willaert, A., Willemsen, M.H., Willems, M., Zuffardi, O., Coucke, P., Speleman, F., Eichler, E.E., Kleefstra, T., and Menten, B. more...
Abstract: Item does not contain fulltext, PURPOSE: Submicroscopic deletions of chromosome band 2p25.3 are associated with intellectual disability and/or central obesity. Although MYT1L is believed to be a critical gene responsible for intellectual disability, so far no unequivocal data have confirmed this hypothesis. METHODS: In this study we evaluated a cohort of 22 patients (15 sporadic patients and two families) with a 2p25.3 aberration to further refine the clinical phenotype and to delineate the role of MYT1L in intellectual disability and obesity. In addition, myt1l spatiotemporal expression in zebrafish embryos was analyzed by quantitative polymerase chain reaction and whole-mount in situ hybridization. RESULTS: Complete MYT1L deletion, intragenic deletion, or duplication was observed in all sporadic patients, in addition to two patients with a de novo point mutation in MYT1L. The familial cases comprise a 6-Mb deletion in a father and his three children and a 5' MYT1L overlapping duplication in a father and his two children. Expression analysis in zebrafish embryos shows specific myt1l expression in the developing brain. CONCLUSION: Our data strongly strengthen the hypothesis that MYT1L is the causal gene for the observed syndromal intellectual disability. Moreover, because 17 patients present with obesity/overweight, haploinsufficiency of MYT1L might predispose to weight problems with childhood onset.Genet Med 17 6, 460-466. more...
Published: 2015

82. Search for ReCQL4 mutations in 39 patients genotyped for suspected Rothmund-Thomson/Baller-Gerold syndromes

Author: UCL - (SLuc) Centre de génétique médicale UCL, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Piard, J., Aral, B., Vabres, P., Holder-Espinasse, M., Mégarbané, A., Gauthier, S., Capra, V., Pierquin, G., Callier, P., Baumann, C., Pasquier, L., Baujat, G., Martorell, L., Rodriguez, A., Brady, A.F., Boralevi, F., González-Enseñat, M.A., Rio, M., Bodemer, C., Philip, N., Cordier, M.-P., Goldenberg, A., Demeer, B., Wright, M., Blair, E., Puzenat, E., Parent, P., Sznajer, Yves, Francannet, C., Didonato, N., Boute, O., Barlogis, V., Moldovan, O., Bessis, D., Coubes, C., Tardieu, M., Cormier-Daire, V., Sousa, A.B., Franques, J., Toutain, A., Tajir, M., Elalaoui, S.C., Geneviève, D., Thevenon, J., Courcet, J.-B., Rivière, J.-B., Collet, C., Gigot, N., Faivre, L., Thauvin-Robinet, C., UCL - (SLuc) Centre de génétique médicale UCL, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Piard, J., Aral, B., Vabres, P., Holder-Espinasse, M., Mégarbané, A., Gauthier, S., Capra, V., Pierquin, G., Callier, P., Baumann, C., Pasquier, L., Baujat, G., Martorell, L., Rodriguez, A., Brady, A.F., Boralevi, F., González-Enseñat, M.A., Rio, M., Bodemer, C., Philip, N., Cordier, M.-P., Goldenberg, A., Demeer, B., Wright, M., Blair, E., Puzenat, E., Parent, P., Sznajer, Yves, Francannet, C., Didonato, N., Boute, O., Barlogis, V., Moldovan, O., Bessis, D., Coubes, C., Tardieu, M., Cormier-Daire, V., Sousa, A.B., Franques, J., Toutain, A., Tajir, M., Elalaoui, S.C., Geneviève, D., Thevenon, J., Courcet, J.-B., Rivière, J.-B., Collet, C., Gigot, N., Faivre, L., and Thauvin-Robinet, C. more...
Abstract: Three overlapping conditions, namely Rothmund-Thomson (RTS), Baller-Gerold (BGS) and RAPADILINO syndromes, have been attributed to RECQL4 mutations. Differential diagnoses depend on the clinical presentation, but the numbers of known genes remain low, leading to the widespread prescription of RECQL4 sequencing. The aim of our study was therefore to determine the best clinical indicators for the presence of RECQL4 mutations in a series of 39 patients referred for RECQL4 molecular analysis and belonging to the RTS (27 cases) and BGS (12 cases) spectrum. One or two deleterious RECQL4 mutations were found in 10/27 patients referred for RTS diagnosis. Clinical and molecular reevaluation led to a different diagnosis in 7/17 negative cases, including Clericuzio-type poikiloderma with neutropenia, hereditary sclerosing poikiloderma, and craniosynostosis/anal anomalies/porokeratosis. No RECQL4 mutations were found in the BGS group without poikiloderma, confirming that RECQL4 sequencing was not indicated in this phenotype. One chromosomal abnormality and one TWIST mutation was found in this cohort. This study highlights the search for differential diagnoses before the prescription of RECQL4 sequencing in this clinically heterogeneous group. The combination of clinically defined subgroups and next-generation sequencing will hopefully bring to light new molecular bases of syndromes with poikiloderma, as well as BGS without poikiloderma. more...
Published: 2015

83. Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d'étude des Tumeurs Endocrines study

Author: Thevenon, J, primary, Bourredjem, A, additional, Faivre, L, additional, Cardot-Bauters, C, additional, Calender, A, additional, Le Bras, M, additional, Giraud, S, additional, Niccoli, P, additional, Odou, M F, additional, Borson-Chazot, F, additional, Barlier, A, additional, Lombard-Bohas, C, additional, Clauser, E, additional, Tabarin, A, additional, Pasmant, E, additional, Chabre, O, additional, Castermans, E, additional, Ruszniewski, P, additional, Bertherat, J, additional, Delemer, B, additional, Christin-Maitre, S, additional, Beckers, A, additional, Guilhem, I, additional, Rohmer, V, additional, Goichot, B, additional, Caron, P, additional, Baudin, E, additional, Chanson, P, additional, Groussin, L, additional, Du Boullay, H, additional, Weryha, G, additional, Lecomte, P, additional, Schillo, F, additional, Bihan, H, additional, Archambeaud, F, additional, Kerlan, V, additional, Bourcigaux, N, additional, Kuhn, J M, additional, Vergès, B, additional, Rodier, M, additional, Renard, M, additional, Sadoul, J L, additional, Binquet, C, additional, and Goudet, P, additional more...
Published: 2015
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84. Clinical reappraisal of SHORT syndrome withPIK3R1mutations: toward recommendation for molecular testing and management

Author: Avila, M., primary, Dyment, D.A., additional, Sagen, J.V., additional, St-Onge, J., additional, Moog, U., additional, Chung, B.H.Y., additional, Mo, S., additional, Mansour, S., additional, Albanese, A., additional, Garcia, S., additional, Martin, D.O., additional, Lopez, A.A., additional, Claudi, T., additional, König, R., additional, White, S.M., additional, Sawyer, S.L., additional, Bernstein, J.A., additional, Slattery, L., additional, Jobling, R.K., additional, Yoon, G., additional, Curry, C.J., additional, Merrer, M.L., additional, Luyer, B.L., additional, Héron, D., additional, Mathieu-Dramard, M., additional, Bitoun, P., additional, Odent, S., additional, Amiel, J., additional, Kuentz, P., additional, Thevenon, J., additional, Laville, M., additional, Reznik, Y., additional, Fagour, C., additional, Nunes, M.-L., additional, Delesalle, D., additional, Manouvrier, S., additional, Lascols, O., additional, Huet, F., additional, Binquet, C., additional, Faivre, L., additional, Rivière, J.-B., additional, Vigouroux, C., additional, Njølstad, P.R., additional, Innes, A.M., additional, and Thauvin-Robinet, C., additional more...
Published: 2015
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85. PRM71 - Using Observational Data From Registry In Cost-Effectiveness Evaluation of Metastatic Castration Resistant Prostate Cancer In France

Author: Leleu, H, Wapenaar, R, Klumper, E, Capone, C, de Beaucoudrey, L, Thevenon, J, and Chevalier, J
Published: 2017
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86. PHS105 - Measuring The Intensity Of Care Coordination For Blood Cancer Patients In France

Author: Mercier, G, Duflos, C, Kanouni, T, Chevalier, J, Thevenon, J, and Cartron, G
Published: 2017
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87. Auditing of batch processes

Author: Maenhout, Greet, DECHAMP, L, THEVENON, J, and DRANSART, P
Subjects: Technology and Engineering
Published: 2004

88. Systematic molecular and cytogenetic screening of 100 patients with marfanoid syndromes and intellectual disability

Author: UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Centre de génétique médicale UCL, Callier, P, Aral, B, Hanna, N, Lambert, S, Dindy, H, Ragon, C, Payet, M, Collod-Beroud, G, Carmignac, V, Delrue, M A, Goizet, C, Philip, N, Busa, T, Dulac, Y, Missotte, I, Sznajer, Yves, Toutain, A, Francannet, C, Megarbane, A, Julia, S, Edouard, T, Sarda, P, Amiel, J, Lyonnet, S, Cormier-Daire, V, Gilbert, B, Jacquette, A, Heron, D, Collignon, P, Lacombe, D, Morice-Picard, F, Jouk, P S, Cusin, V, Willems, M, Sarrazin, E, Amarof, K, Coubes, C, Addor, M C, Journel, H, Colin, E, Khau Van Kien, P, Baumann, C, Leheup, B, Martin-Coignard, D, Doco-Fenzy, M, Goldenberg, A, Plessis, G, Thevenon, J, Pasquier, L, Odent, S, Vabres, P, Huet, F, Marle, N, Mosca-Boidron, A L, Mugneret, F, Gauthier, S, Binquet, C, Thauvin-Robinet, C, Jondeau, G, Boileau, C, Faivre, L, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Centre de génétique médicale UCL, Callier, P, Aral, B, Hanna, N, Lambert, S, Dindy, H, Ragon, C, Payet, M, Collod-Beroud, G, Carmignac, V, Delrue, M A, Goizet, C, Philip, N, Busa, T, Dulac, Y, Missotte, I, Sznajer, Yves, Toutain, A, Francannet, C, Megarbane, A, Julia, S, Edouard, T, Sarda, P, Amiel, J, Lyonnet, S, Cormier-Daire, V, Gilbert, B, Jacquette, A, Heron, D, Collignon, P, Lacombe, D, Morice-Picard, F, Jouk, P S, Cusin, V, Willems, M, Sarrazin, E, Amarof, K, Coubes, C, Addor, M C, Journel, H, Colin, E, Khau Van Kien, P, Baumann, C, Leheup, B, Martin-Coignard, D, Doco-Fenzy, M, Goldenberg, A, Plessis, G, Thevenon, J, Pasquier, L, Odent, S, Vabres, P, Huet, F, Marle, N, Mosca-Boidron, A L, Mugneret, F, Gauthier, S, Binquet, C, Thauvin-Robinet, C, Jondeau, G, Boileau, C, and Faivre, L more...
Abstract: The association of marfanoid habitus (MH) and intellectual disability (ID) has been reported in the literature, with overlapping presentations and genetic heterogeneity. A hundred patients (71 males and 29 females) with a MH and ID were recruited. Custom-designed 244K array-CGH (Agilent®; Agilent Technologies Inc., Santa Clara, CA) and MED12, ZDHHC9, UPF3B, FBN1, TGFBR1 and TGFBR2 sequencing analyses were performed. Eighty patients could be classified as isolated MH and ID: 12 chromosomal imbalances, 1 FBN1 mutation and 1 possibly pathogenic MED12 mutation were found (17%). Twenty patients could be classified as ID with other extra-skeletal features of the Marfan syndrome (MFS) spectrum: 4 pathogenic FBN1 mutations and 4 chromosomal imbalances were found (2 patients with both FBN1 mutation and chromosomal rearrangement) (29%). These results suggest either that there are more loci with genes yet to be discovered or that MH can also be a relatively non-specific feature of patients with ID. The search for aortic complications is mandatory even if MH is associated with ID since FBN1 mutations or rearrangements were found in some patients. The excess of males is in favour of the involvement of other X-linked genes. Although it was impossible to make a diagnosis in 80% of patients, these results will improve genetic counselling in families. more...
Published: 2013

89. Search forReCQL4mutations in 39 patients genotyped for suspected Rothmund-Thomson/Baller-Gerold syndromes

Author: Piard, J., primary, Aral, B., additional, Vabres, P., additional, Holder‐Espinasse, M., additional, Mégarbané, A., additional, Gauthier, S., additional, Capra, V., additional, Pierquin, G., additional, Callier, P., additional, Baumann, C., additional, Pasquier, L., additional, Baujat, G., additional, Martorell, L., additional, Rodriguez, A., additional, Brady, A. F., additional, Boralevi, F., additional, González‐Enseñat, M. A., additional, Rio, M., additional, Bodemer, C., additional, Philip, N., additional, Cordier, M.‐P., additional, Goldenberg, A., additional, Demeer, B., additional, Wright, M., additional, Blair, E., additional, Puzenat, E., additional, Parent, P., additional, Sznajer, Y., additional, Francannet, C., additional, DiDonato, N., additional, Boute, O., additional, Barlogis, V., additional, Moldovan, O., additional, Bessis, D., additional, Coubes, C., additional, Tardieu, M., additional, Cormier‐Daire, V., additional, Sousa, A. B., additional, Franques, J., additional, Toutain, A., additional, Tajir, M., additional, Elalaoui, S. C., additional, Geneviève, D., additional, Thevenon, J., additional, Courcet, J.‐B., additional, Rivière, J.‐B., additional, Collet, C., additional, Gigot, N., additional, Faivre, L., additional, and Thauvin‐Robinet, C., additional more...
Published: 2014
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90. Infection par la chlamydiose aviaire chez les pigeons d'élevage en Nouvelle-Calédonie

Author: Thevenon, J, Rantoen, D, Carton, D, Costa, R, Trap, D, and Revues Inra, Import
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.BA] Life Sciences [q-bio]/Animal biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, ComputingMilieux_MISCELLANEOUS
Published: 1992

91. Two-year study of endemic enteric pathogens associated with acute diarrhea in New Caledonia

Author: Germani, Y, primary, Morillon, M, additional, Begaud, E, additional, Dubourdieu, H, additional, Costa, R, additional, and Thevenon, J, additional
Published: 1994
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92. Dense pixel matching between unrectified and distorted images using dynamic programming

Author: Thevenon, J., Jesús Martínez del Rincón, Dieny, R., and Nebel, J. -C

93. Bioinformatics inspired algorithm for stereo correspondence

Author: Dieny, R., Thevenon, J., Martinez-Del-Rincon, J., and Jean-Christophe Nebel

94. 151 Postzygotic KITLGmutation in a congenital non-progressive linear nevoid hyperpigmentation

Author: Sorlin, A., Maruani, A., Rivière, J., Duffourd, Y., Kuentz, P., Jouan, T., Thauvin-Robinet, C., Thevenon, J., Faivre, L., and Vabres, P.
Published: 2016
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95. De novo SMARCA2 variants clustered outside the helicase domain cause a new recognizable syndrome with intellectual disability and blepharophimosis distinct from Nicolaides-Baraitser syndrome

Author: Gerarda Cappuccio, Camille Sayou, Pauline Le Tanno, Emilie Tisserant, Ange-Line Bruel, Sara El Kennani, Joaquim Sá, Karen J. Low, Cristina Dias, Markéta Havlovicová, Miroslava Hančárová, Evan E. Eichler, Françoise Devillard, Sébastien Moutton, Julien Van-Gils, Christèle Dubourg, Sylvie Odent, Bénédicte Gerard, Amélie Piton, Toshiyuki Yamamoto, Nobuhiko Okamoto, Helen Firth, Kay Metcalfe, Anna Moh, Kimberly A. Chapman, Erfan Aref-Eshghi, Jennifer Kerkhof, Annalaura Torella, Vincenzo Nigro, Laurence Perrin, Juliette Piard, Gwenaël Le Guyader, Thibaud Jouan, Christel Thauvin-Robinet, Yannis Duffourd, Jaya K. George-Abraham, Catherine A. Buchanan, Denise Williams, Usha Kini, Kate Wilson, Nicola Brunetti-Pierri, Giorgio Casari, Michele Pinelli, Francesco Musacchia, Margherita Mutarelli, Diego Carrella, Giuseppina Vitiello, Valeria Capra, Giancarlo Parenti, Vincenzo Leuzzi, Angelo Selicorni, Silvia Maitz, Sandro Banfi, Marcella Zollino, Mario Montomoli, Donatelli Milani, Corrado Romano, Albina Tummolo, Daniele De Brasi, Antonietta Coppola, Claudia Santoro, Angela Peron, Chiara Pantaleoni, Raffaele Castello, Stefano D’Arrigo, Sérgio B. Sousa, Raoul C.M. Hennekam, Bekim Sadikovic, Julien Thevenon, Jérôme Govin, Antonio Vitobello, Università degli studi di Napoli Federico II, 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), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospital Motol [Prague], University of Washington [Seattle], Centre Hospitalier Universitaire [Grenoble] (CHU), Université de Bordeaux (UB), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), London Health Sciences Center (LHSC), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Equipe GAD (LNC - U1231), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), GSP15001, Fondazione Telethon, 209568/Z/17/Z, Wellcome Trust, Cappuccio, G., Sayou, C., Tanno, P. L., Tisserant, E., Bruel, A. -L., Kennani, S. E., Sa, J., Low, K. J., Dias, C., Havlovicova, M., Hancarova, M., Eichler, E. E., Devillard, F., Moutton, S., Van-Gils, J., Dubourg, C., Odent, S., Gerard, B., Piton, A., Yamamoto, T., Okamoto, N., Firth, H., Metcalfe, K., Moh, A., Chapman, K. A., Aref-Eshghi, E., Kerkhof, J., Torella, A., Nigro, V., Perrin, L., Piard, J., Le Guyader, G., Jouan, T., Thauvin-Robinet, C., Duffourd, Y., George-Abraham, J. K., Buchanan, C. A., Williams, D., Kini, U., Wilson, K., Brunetti-Pierri, N., Casari, G., Pinelli, M., Musacchia, F., Mutarelli, M., Carrella, D., Vitiello, G., Capra, V., Parenti, G., Leuzzi, V., Selicorni, A., Maitz, S., Banfi, S., Zollino, M., Montomoli, M., Milani, D., Romano, C., Tummolo, A., De Brasi, D., Coppola, A., Santoro, C., Peron, A., Pantaleoni, C., Castello, R., D'Arrigo, S., Sousa, S. B., Hennekam, R. C. M., Sadikovic, B., Thevenon, J., Govin, J., Vitobello, A., University of Naples Federico II = Università degli studi di Napoli Federico II, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, 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 ), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, General Paediatrics, APH - Quality of Care, and Brunetti-Pierri, Nicola more...
Subjects: Foot Deformities, Foot Deformities, Congenital, [SDV]Life Sciences [q-bio], Biology, Blepharophimosis, Settore MED/03 - GENETICA MEDICA, Hypotrichosis, Chromatin remodeling, 03 medical and health sciences, Congenital, 0302 clinical medicine, Neurodevelopmental disorder, Intellectual Disability, Intellectual disability, SMARCA2, medicine, Humans, Gene, Genetics (clinical), 030304 developmental biology, Genetics, 0303 health sciences, BIS, Facies, medicine.disease, Phenotype, neurodevelopmental disorder, Nicolaides–Baraitser syndrome, intellectual disability, DNA methylation, 030217 neurology & neurosurgery, Transcription Factors
Abstract: International audience; Purpose: Nontruncating variants in SMARCA2, encoding a catalytic subunit of SWI/SNF chromatin remodeling complex, cause Nicolaides-Baraitser syndrome (NCBRS), a condition with intellectual disability and multiple congenital anomalies. Other disorders due to SMARCA2 are unknown.Methods: By next-generation sequencing, we identified candidate variants in SMARCA2 in 20 individuals from 18 families with a syndromic neurodevelopmental disorder not consistent with NCBRS. To stratify variant interpretation, we functionally analyzed SMARCA2 variants in yeasts and performed transcriptomic and genome methylation analyses on blood leukocytes.Results: Of 20 individuals, 14 showed a recognizable phenotype with recurrent features including epicanthal folds, blepharophimosis, and downturned nasal tip along with variable degree of intellectual disability (or blepharophimosis intellectual disability syndrome [BIS]). In contrast to most NCBRS variants, all SMARCA2 variants associated with BIS are localized outside the helicase domains. Yeast phenotype assays differentiated NCBRS from non-NCBRS SMARCA2 variants. Transcriptomic and DNA methylation signatures differentiated NCBRS from BIS and those with nonspecific phenotype. In the remaining six individuals with nonspecific dysmorphic features, clinical and molecular data did not permit variant reclassification.Conclusion: We identified a novel recognizable syndrome named BIS associated with clustered de novo SMARCA2 variants outside the helicase domains, phenotypically and molecularly distinct from NCBRS. more...
Published: 2020
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96. First presentation of fractures and bone healing in pediatric KBG Syndrome

Author: Aurélien Courvoisier, Marco Bigoni, Marco Turati, Lilia Brahim, Brice Poreau, Giovanni Zatti, Andrea Cossio, Julien Thevenon, Turati, M, Brahim, L, Thevenon, J, Poreau, B, Cossio, A, Zatti, G, Bigoni, M, and Courvoisier, A more...
Subjects: medicine.medical_specialty, business.industry, Humeru, Bone healing, KBG SYNDROME, Surgery, medicine.anatomical_structure, Bone fracture, KBG Syndrome, Mutation (genetic algorithm), Mutation, medicine, Orthopedics and Sports Medicine, Humerus, Presentation (obstetrics), business, Child
Abstract: KBG Syndrome is a rare syndrome characterized by facial and hand anomalies, postnatal short stature, delayed bone age, intellectual disability and macrodontia. A key role of mutations in ANRKD11 gene was observed not only in central nervous system but also in skeletal development and function. Indeed, a meticulous evaluation of bone metabolism was recommended in KBG Syndrome. We report on a 11-year-old female child affected by KBG Syndrome with a diaphyseal transverse humeral fracture treated surgically and a clavicular fracture treated conservatively. Bone consolidation was observed in both fractures. To the best of our knowledge, no fracture and bone healing were accurately described in KBG patients. Bone healing was observed after surgical treatment of a humeral diaphyseal fracture and after a conservative treatment of a clavicle fracture. These results showed that bone healing was possible also in presence of a mutation of ANKRD11 gene, an important gene in bone metabolism. more...
Published: 2020

97. The landscape of epilepsy-related GATOR1 variants

Author: Johannes R. Lemke, Pia Zacher, Thomas Dorn, Laura Hernandez-Hernandez, Natasha E. Schoeler, Stéphanie Baulac, Sara Baldassari, Anne de Saint Martin, Eleni Panagiotakaki, Anne Fabienne Lepine, Markus Wolff, Arnaud Biraben, Renske Oegema, Edouard Hirsch, Anna Jansen, Charles Deckers, Nienke E. Verbeek, Fabienne Picard, Georg Dorfmüller, Sarah Ferrand-Sorbets, Barbora Benova, Francesca Bisulli, Inga Talvik, Kristin Lindstrom, Tilman Polster, Douglas R. Nordli, Tommaso Pippucci, Eva H. Brilstra, Shifteh Sattar, Erik H. Niks, Marie Line Jacquemont, Kees P.J. Braun, Karen Müller-Schlüter, Sanjay M. Sisodiya, Sarah Weckhuysen, Lysa Boissé Lomax, Sophie Julia, Brigitte Ricard-Mousnier, Mathilde Chipaux, Laura Licchetta, Gaetan Lesca, Bianca Berghuis, S. Krithika, Jamel Chelly, Renzo Guerrini, Hélène Catenoix, Annapurna Poduri, Melanie Jennesson, Pasquale Striano, Rikke S. Møller, Antonio Gambardella, Guillaume Achaz, Peter Uldall, Fabrice Bartolomei, Giuseppe d'Orsi, Laurence Faivre, Floor E. Jansen, An Sofie Schoonjans, Kevin Rostasy, Thomas Becher, Pavel Krsek, Julien Thevenon, Marjan J. A. van Kempen, Guido Rubboli, Cécile Marchal, Meral Balci, Boudewijn Gunning, Ilona Krey, Julitta de Bellescize, Veronique Darmency, Christopher J. Yuskaitis, Daniëlle de Jong, Giovanni Crichiutti, Paolo Tinuper, Katrien Stouffs, Valentin Sander, Anne-Sophie Lebre, Thomas Cloppenborg, Valerio Conti, Gabrielle Rudolf, Courtney Kiss, Eveline Hagebeuk, Caroline Nava, Eric LeGuern, Ilse Wegner, Christian Brandt, Martin Zenker, Simona Balestrini, Picard, Fabienne, Baldassari S., Picard F., Verbeek N.E., van Kempen M., Brilstra E.H., Lesca G., Conti V., Guerrini R., Bisulli F., Licchetta L., Pippucci T., Tinuper P., Hirsch E., de Saint Martin A., Chelly J., Rudolf G., Chipaux M., Ferrand-Sorbets S., Dorfmuller G., Sisodiya S., Balestrini S., Schoeler N., Hernandez-Hernandez L., Krithika S., Oegema R., Hagebeuk E., Gunning B., Deckers C., Berghuis B., Wegner I., Niks E., Jansen F.E., Braun K., de Jong D., Rubboli G., Talvik I., Sander V., Uldall P., Jacquemont M.-L., Nava C., Leguern E., Julia S., Gambardella A., d'Orsi G., Crichiutti G., Faivre L., Darmency V., Benova B., Krsek P., Biraben A., Lebre A.-S., Jennesson M., Sattar S., Marchal C., Nordli D.R., Lindstrom K., Striano P., Lomax L.B., Kiss C., Bartolomei F., Lepine A.F., Schoonjans A.-S., Stouffs K., Jansen A., Panagiotakaki E., Ricard-Mousnier B., Thevenon J., de Bellescize J., Catenoix H., Dorn T., Zenker M., Muller-Schluter K., Brandt C., Krey I., Polster T., Wolff M., Balci M., Rostasy K., Achaz G., Zacher P., Becher T., Cloppenborg T., Yuskaitis C.J., Weckhuysen S., Poduri A., Lemke J.R., Moller R.S., Baulac S., Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Genetics [Utrecht, the Netherlands], University Medical Center [Utrecht], Service de Génétique [HCL Groupement Hospitalier Est], Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Children's Hospital A. Meyer, Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Clinical and Experimental Epilepsy, University College of London [London] (UCL), Academic Center for Epileptology Kempenhaeghe & Maastricht UMC+ [Heeze], Danish Epilepsy Centre, Denmark and Aarhus University, Aarhus, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de génétique médicale [Toulouse], CHU Toulouse [Toulouse], Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), FHU TRANSLAD (CHU de Dijon), Université de Bourgogne (UB), Service de Neurophysiologie Clinique (CHU Dijon), CHU Pontchaillou [Rennes], Service de pédiatrie spécialisée et médecine infantile (neurologie, pneumologie, maladies héréditaires du métabolisme) [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Epilepsie, sommeil et explorations fonctionnelles neuropédiatriques, Hospices Civils de Lyon (HCL)-Hôpital Femme Mère Enfant, Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Bourgogne Franche-Comté [COMUE] (UBFC), Département d'Epilepsie, Sommeil et Neurophysiologie Pédiatrique [HCL, Lyon], Hospices Civils de Lyon (HCL), Institute of Human Genetics, University Hospital Magdeburg, Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupement hospitalier Lyon-Est, Centre de recherche en neurosciences de Lyon (CRNL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse] more...
Subjects: Male, 0301 basic medicine, Proband, DEPDC5, SUDEP, 030105 genetics & heredity, Bioinformatics, Loss of Function Mutation/genetics, Epilepsy, INDEL Mutation, Loss of Function Mutation, mTORC1 pathway, Genetics(clinical), Child, Genetics (clinical), Multiprotein Complexes/genetics, Brugada Syndrome, DNA Copy Number Variation, Brugada syndrome, INDEL Mutation/genetics, GTPase-Activating Proteins, NPRL3, Seizure, Phenotype, Pedigree, 3. Good health, Brugada Syndrome/genetics, Child, Preschool, Female, Human, Signal Transduction, DNA Copy Number Variations, Adolescent, Seizures/complications, Mechanistic Target of Rapamycin Complex 1/genetics, DNA Copy Number Variations/genetics, Mechanistic Target of Rapamycin Complex 1, Tumor Suppressor Proteins/genetics, Article, Focal cortical dysplasia, 03 medical and health sciences, Seizures, GTPase-Activating Proteins/genetics, medicine, Humans, Genetic Predisposition to Disease, Genetic focal epilepsy, Epilepsy/complications, Repressor Proteins/genetics, business.industry, GTPase-Activating Protein, Tumor Suppressor Proteins, Infant, Newborn, Correction, Infant, Repressor Protein, Cortical dysplasia, medicine.disease, ddc:616.8, Repressor Proteins, 030104 developmental biology, Frontal lobe seizures, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Multiprotein Complexes, Multiprotein Complexe, Signal Transduction/genetics, Human medicine, business
Abstract: Purpose:\ud \ud To define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative regulator of the mTORC1 pathway.\ud \ud Methods:\ud \ud We analyzed clinical and genetic data of 73 novel probands (familial and sporadic) with epilepsy-related variants in GATOR1-encoding genes and proposed new guidelines for clinical interpretation of GATOR1 variants.\ud \ud Results:\ud \ud The GATOR1 seizure phenotype consisted mostly in focal seizures (e.g., hypermotor or frontal lobe seizures in 50%), with a mean age at onset of 4.4 years, often sleep-related and drug-resistant (54%), and associated with focal cortical dysplasia (20%). Infantile spasms were reported in 10% of the probands. Sudden unexpected death in epilepsy (SUDEP) occurred in 10% of the families. Novel classification framework of all 140 epilepsy-related GATOR1 variants (including the variants of this study) revealed that 68% are loss-of-function pathogenic, 14% are likely pathogenic, 15% are variants of uncertain significance and 3% are likely benign.\ud \ud Conclusion:\ud \ud Our data emphasize the increasingly important role of GATOR1 genes in the pathogenesis of focal epilepsies (>180 probands to date). The GATOR1 phenotypic spectrum ranges from sporadic early-onset epilepsies with cognitive impairment comorbidities to familial focal epilepsies, and SUDEP. more...
Published: 2018
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98. Fifteen years of research on oral-facial-digital syndromes: from 1 to 16 causal genes

Author: Nadège Gigot, Anne Dieux, Yannis Duffourd, Bernard Aral, Lydie Burglen, Bérénice Doray, Olivier Rosnet, Alice Goldenberg, Martijn A. Huynen, Oliver E. Blacque, Brunella Franco, André Mégarbané, Diane Doummar, Ernie M.H.F. Bongers, Anne Fargeot-Espaliat, Clarisse Baumann, Judith St-Onge, Daniel Birnbaum, Sophie Saunier, Thibaut Eguether, Jean-François Deleuze, Estelle Lopez, Dominique Gaillard, Geneviève Pierquin, Shubha R. Phadke, Michel R. Leroux, Rachel H. Giles, Tania Attié-Bitach, Jaclyn S. Goldstein, Isabelle Desguerres, Elisabeth Steichen-Gersdorf, Brigitte Gilbert-Dussardier, Manuela Morleo, Jesús Argente, Jean Baptiste Rivière, Gregory J. Pazour, Christel Thauvin-Robinet, Julien Thevenon, Albert David, Maxence V. Nachury, Laurence Faivre, Philippe Loget, Véronique Chevrier, Bruno Reversade, Laurence Jego, Ange Line Bruel, Vicente Herranz-Pérez, Laurent Pasquier, Colin A. Johnson, John B. Wallingford, Valérie Cormier-Daire, Inusha Panigrahi, Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut d'Astrophysique et de Géophysique [Liège], Université de Liège, FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service: neuropédiatrie pathologie du développement, Université Pierre et Marie Curie - Paris 6 (UPMC), University Medical Center [Utrecht], University of Leeds, Radboud University [Nijmegen], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Génétique Humaine, Université de Liège-CHU Liège, Service de Génétique, Hôpital de Hautepierre [Strasbourg], Génétique Médicale, Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre de Référence Anomalies du Développement Ouest, Laboratory of Human Embryology and Genetics, Institute of Medical Biology, Singapore, Department of Pediatrics, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Département de Génétique Médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Advanced Pediatric Center (PGIMER), Pediatry center, Pédiatrie Neonatalogie, Centre Hospitalier Général, Brive-la-Gaillarde, Brive-la-Gaillarde, France, Service de Génétique clinique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Dauphine Recherches en Management - MLAB (DRM - MLAB), Dauphine Recherches en Management (DRM), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Department of human genetics, Radboud University Medical Center [Nijmegen]-Nijmegen Centre for Molecular Life Sciences-Institute for Genetic and Metabolic Disorders, Centre de génétique et Centre de référence maladies rares et anomalies du développement et syndromes malformatifs du Centre Est, Département de Génétique et Procréation UF-Hôpital Couple Enfant de Grenoble-CHU Grenoble, Hospital Universitario La Paz, Laboratoire de Génétique Chromosomique et Moléculaire [CHU Dijon], FHU TRANSLAD, Département de Génétique, Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India, Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie intégrative de la molécule à l'organisme, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Neuropathies héréditaires et rein en développement, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de génétique médicale, Université Saint-Joseph de Beyrouth (USJ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), FHU TRANSLAD, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Génétique des Anomalies du Développement ( GAD ), IFR100 - Structure fédérative de recherche Santé-STIC-Université de Bourgogne ( UB ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands, Section of Ophthalmology and Neurosciences, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK, Radboud university [Nijmegen], Centre de Recherche en Cancérologie de Marseille ( CRCM ), Aix Marseille Université ( AMU ) -Institut Paoli-Calmettes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de neuropédiatrie et pathologie du développement, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Service de neurométabolisme, Hôpital Necker-Enfants Malades, CHU, Paris, France, CHU de Poitiers-Centre de Référence Anomalies du Développement Ouest, Innsbruck Medical University [Austria] ( IMU ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Advanced Pediatric Center ( PGIMER ), Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Dauphine Recherches en Management - MLAB ( DRM - MLAB ), Dauphine Recherches en Management ( DRM ), Université Paris-Dauphine-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Dauphine-Centre National de la Recherche Scientifique ( CNRS ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Service d'anatomie et cytologie pathologiques [Rennes], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Saint-Joseph de Beyrouth ( USJ ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Innsbruck Medical University [Austria] (IMU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Centre National de la Recherche Scientifique (CNRS)-Université Paris Dauphine-PSL-Centre National de la Recherche Scientifique (CNRS)-Université Paris Dauphine-PSL, Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Bruel, Ange Line, Franco, Brunella, Duffourd, Yanni, Thevenon, Julien, Jego, Laurence, Lopez, Estelle, Deleuze, Jean Françoi, Doummar, Diane, Giles, Rachel H, Johnson, Colin A, Huynen, Martijn A, Chevrier, Véronique, Burglen, Lydie, Morleo, Manuela, Desguerres, Isabelle, Pierquin, Geneviève, Doray, Bérénice, Gilbert Dussardier, Brigitte, Reversade, Bruno, Steichen Gersdorf, Elisabeth, Baumann, Clarisse, Panigrahi, Inusha, Fargeot Espaliat, Anne, Dieux, Anne, David, Albert, Goldenberg, Alice, Bongers, Ernie, Gaillard, Dominique, Argente, Jesú, Aral, Bernard, Gigot, Nadège, St Onge, Judith, Birnbaum, Daniel, Phadke, Shubha R, Cormier Daire, Valérie, Eguether, Thibaut, Pazour, Gregory J, Herranz Pérez, Vicente, Goldstein, Jaclyn S, Pasquier, Laurent, Loget, Philippe, Saunier, Sophie, Mégarbané, André, Rosnet, Olivier, Leroux, Michel R, Wallingford, John B, Blacque, Oliver E, Nachury, Maxence V, Attie Bitach, Tania, Rivière, Jean Baptiste, Faivre, Laurence, Thauvin Robinet, Christel, Bruel, Al, Franco, B, Duffourd, Y, Thevenon, J, Jego, L, Lopez, E, Deleuze, Jf, Doummar, D, Giles, Rh, Johnson, Ca, Huynen, Ma, Chevrier, V, Burglen, L, Morleo, M, Desguerres, I, Pierquin, G, Doray, B, Gilbert-Dussardier, B, Reversade, B, Steichen-Gersdorf, E, Baumann, C, Panigrahi, I, Fargeot-Espaliat, A, Dieux, A, David, A, Goldenberg, A, Bongers, E, Gaillard, D, Argente, J, Aral, B, Gigot, N, St-Onge, J, Birnbaum, D, Phadke, Sr, Cormier-Daire, V, Eguether, T, Pazour, Gj, Herranz-Perez, V, Goldstein, J, Pasquier, L, Loget, P, Saunier, S, Megarbane, A, Rosnet, O, Leroux, Mr, Wallingford, Jb, Blacque, Oe, Nachury, Mv, Attie-Bitach, T, Riviere, Jb, Faivre, L, and Thauvin-Robinet, C more...
Subjects: Male, 0301 basic medicine, Heterozygote, ciliopathie, Oral facial digital, [SDV]Life Sciences [q-bio], [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Biology, Ciliopathies, Centriole elongation, 03 medical and health sciences, Intraflagellar transport, Genotype, Genetics, Polycystic kidney disease, medicine, Humans, Abnormalities, Multiple, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Functional studies, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene, oral-facial-digital syndromes, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Encephalocele, Polycystic Kidney Diseases, [ SDV ] Life Sciences [q-bio], ciliopathies, Proteins, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Orofaciodigital Syndromes, medicine.disease, 030104 developmental biology, Face, Mutation, Female, Retinitis Pigmentosa, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Ciliary Motility Disorders
Abstract: Oral–facial–digital syndromes (OFDS) gather rare genetic disorders characterised by facial, oral and digital abnormalities associated with a wide range of additional features (polycystic kidney disease, cerebral malformations and several others) to delineate a growing list of OFDS subtypes. The most frequent, OFD type I, is caused by a heterozygous mutation in theOFD1gene encoding a centrosomal protein. The wide clinical heterogeneity of OFDS suggests the involvement of other ciliary genes. For 15 years, we have aimed to identify the molecular bases of OFDS. This effort has been greatly helped by the recent development of whole-exome sequencing (WES). Here, we present all our published and unpublished results for WES in 24 cases with OFDS. We identified causal variants in five new genes (C2CD3,TMEM107,INTU,KIAA0753andIFT57) and related the clinical spectrum of four genes in other ciliopathies (C5orf42,TMEM138,TMEM231andWDPCP) to OFDS. Mutations were also detected in two genes previously implicated in OFDS. Functional studies revealed the involvement of centriole elongation, transition zone and intraflagellar transport defects in OFDS, thus characterising three ciliary protein modules: the complex KIAA0753-FOPNL-OFD1, a regulator of centriole elongation; the Meckel-Gruber syndrome module, a major component of the transition zone; and the CPLANE complex necessary for IFT-A assembly. OFDS now appear to be a distinct subgroup of ciliopathies with wide heterogeneity, which makes the initial classification obsolete. A clinical classification restricted to the three frequent/well-delineated subtypes could be proposed, and for patients who do not fit one of these three main subtypes, a further classification could be based on the genotype. more...
Published: 2017
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99. OFIP/KIAA0753 forms a complex with OFD1 and FOR20 at pericentriolar satellites and centrosomes and is mutated in one individual with oral-facial-digital syndrome

Author: Teunis J. P. van Dam, Angélique Bole, Emilie Baudelet, Christel Thauvin-Robinet, Jean-Baptiste Rivière, Jean-Paul Borg, Olivier Rosnet, Ange-Line Bruel, Melissa Lo Scalzo, Daniel Isnardon, Brunella Franco, Paul Kuentz, Martijn A. Huynen, Daniel Birnbaum, Laurence Faivre, Véronique Chevrier, Stéphane Audebert, Frédérique Lembo, Lydie Burglen, Julien Thevenon, Chevrier, V, Bruel, Al, Van Dam, Tj, Franco, Brunella, Lo Scalzo, M, Lembo, F, Audebert, S, Baudelet, E, Isnardon, D, Bole, A, Borg, Jp, Kuentz, P, Thevenon, J, Burglen, L, Faivre, L, Rivière, Jb, Huynen, Ma, Birnbaum, D, Rosnet, O, Thauvin Robinet, C., Centre de Recherche en Cancérologie de Marseille ( CRCM ), Aix Marseille Université ( AMU ) -Institut Paoli-Calmettes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Paoli Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Génétique des Anomalies du Développement ( GAD ), Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Radboud University Medical Center [Nijmegen], Institut d'Astrophysique et de Géophysique [Liège], Université de Liège, Dipartimento di Scienze Mediche Traslazionali, Università degli studi di Napoli Federico II, Johns Hopkins University ( JHU ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de neuropédiatrie et pathologie du développement, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Service de Génétique et d'Embryologie Médicale, INSERM Institut Paoli-Calmettes GIS-Institut des Maladies Rares (HTS) French Ministry of Health (PHRC national) 2010-A01014-35 Italian Telethon Foundation TGM11CB3 Regional Council of Burgundy European Community's Seventh Framework Programme 241955 SYSCILIA Institut Paoli-Calmettes, Inserm Aix-Marseille University, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), University of Naples Federico II = Università degli studi di Napoli Federico II, Johns Hopkins University (JHU), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU) more...
Subjects: 0301 basic medicine, Centriole, cell-cycle progression, Gene Expression, medicine.disease_cause, Ciliopathies, human-disease gene, molecular characterization, bbs proteins, Genetics (clinical), Conserved Sequence, Centrioles, Genetics, Mutation, Cilium, Ciliary transition zone, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], General Medicine, Orofaciodigital Syndromes, 3. Good health, centriolar satellites, multiple sequence alignment, basal body docking, Female, Microtubule-Associated Proteins, Protein Binding, Heterozygote, Molecular Sequence Data, Biology, 03 medical and health sciences, Intraflagellar transport, Ciliogenesis, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Humans, Amino Acid Sequence, Cilia, Molecular Biology, Centrosome, intraflagellar transport, Base Sequence, Infant, Newborn, Proteins, 030104 developmental biology, ciliary transition zone, Sequence Alignment, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, ciliogenesis
Abstract: Item does not contain fulltext Oral-facial-digital (OFD) syndromes are rare heterogeneous disorders characterized by the association of abnormalities of the face, the oral cavity and the extremities, some due to mutations in proteins of the transition zone of the primary cilia or the closely associated distal end of centrioles. These two structures are essential for the formation of functional cilia, and for signaling events during development. We report here causal compound heterozygous mutations of KIAA0753/OFIP in a patient with an OFD VI syndrome. We show that the KIAA0753/OFIP protein, whose sequence is conserved in ciliated species, associates with centrosome/centriole and pericentriolar satellites in human cells and forms a complex with FOR20 and OFD1. The decreased expression of any component of this ternary complex in RPE1 cells causes a defective recruitment onto centrosomes and satellites. The OFD KIAA0753/OFIP mutant loses its capacity to interact with FOR20 and OFD1, which may be the molecular basis of the defect. We also show that KIAA0753/OFIP has microtubule-stabilizing activity. OFD1 and FOR20 are known to regulate the integrity of the centriole distal end, confirming that this structural element is a target of importance for pathogenic mutations in ciliopathies. more...
Published: 2016
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100. The oral-facial-digital syndrome gene C2CD3 encodes a positive regulator of centriole elongation

Author: Laurent Pasquier, Bernard Aral, Jaclyn S Lee, Judith St-Onge, Michel Vekemans, Frédéric Huet, Brunella Franco, Fan Ye, Philippe Loget, Ange-Line Bruel, Arnold Munnich, Nadège Gigot, Carla A.M. Lopes, Sophie Saunier, José Manuel García-Verdugo, Julien Thevenon, Vicente Herranz-Pérez, Susana González-Granero, Laurence Jego, Maxence V. Nachury, André Mégarbané, Jean-Baptiste Rivière, Laurence Faivre, Caroline Alby, Toshinobu Shida, Christel Thauvin-Robinet, Andrew M. Fry, Estelle Lopez, Tania Attié-Bitach, Thauvin Robinet, C, Lee, J, Lopez, E, Herranz Pérez, V, Shida, T, Franco, Brunella, Jego, L, Ye, F, Pasquier, L, Loget, P, Gigot, N, Aral, B, Lopes, Ca, St Onge, J, Bruel, Al, Thevenon, J, González Granero, S, Alby, C, Munnich, A, Vekemans, M, Huet, F, Fry, Am, Saunier, S, Rivière, Jb, Attié Bitach, T, Garcia Verdugo, Jm, Faivre, L, Mégarbané, A, and Nachury, M. V. more...
Subjects: Male, Microcephaly, Centriole, Microtubule-associated protein, sports, Biology, Ciliopathies, Centriole elongation, Article, Cell Line, Procentriole, Genetics, medicine, Humans, Genetic Predisposition to Disease, Centrioles, Cilium, Proteins, Orofaciodigital Syndromes, medicine.disease, sports.league, HEK293 Cells, Centrosome, Child, Preschool, Microtubule-Associated Proteins
Abstract: Centrioles are microtubule-based, barrel-shaped structures that initiate the assembly of centrosomes and cilia(1,2). How centriole length is precisely set remains elusive. The microcephaly protein CPAP (also known as MCPH6) promotes procentriole growth(3-5), whereas the oral-facial-digital (OFD) syndrome protein OFD1 represses centriole elongation(6,7). Here we uncover a new subtype of OFD with severe microcephaly and cerebral malformations and identify distinct mutations in two affected families in the evolutionarily conserved C2CD3 gene. Concordant with the clinical overlap, C2CD3 colocalizes with OFD1 at the distal end of centrioles, and C2CD3 physically associates with OFD1. However, whereas OFD1 deletion leads to centriole hyperelongation, loss of C2CD3 results in short centrioles without subdistal and distal appendages. Because C2CD3 overexpression triggers centriole hyperelongation and OFD1 antagonizes this activity, we propose that C2CD3 directly promotes centriole elongation and that OFD1 acts as a negative regulator of C2CD3. Our results identify regulation of centriole length as an emerging pathogenic mechanism in ciliopathies. more...
Published: 2014
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