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33 results on '"LONJOU, CHRISTINE"'

1. Gene network and biological pathways associated with susceptibility to differentiated thyroid carcinoma

Author

Kulkarni, Om, Sugier, Pierre-Emmanuel, Guibon, Julie, Boland-Augé, Anne, Lonjou, Christine, Bacq-Daian, Delphine, Olaso, Robert, Rubino, Carole, Souchard, Vincent, Rachedi, Frédérique, Lence-Anta, Juan Jesus, Ortiz, Rosa Maria, Xhaard, Constance, Laurent-Puig, Pierre, Mulot, Claire, Guizard, Anne-Valérie, Schvartz, Claire, Boutron-Ruault, Marie-Christine, Ostroumova, Evgenia, Kesminiene, Ausrele, Deleuze, Jean-François, Guénel, Pascal, De Vathaire, Florent, Truong, Thérèse, and Lesueur, Fabienne

Published
2021
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5. Mutations in IFT172 cause isolated retinal degeneration and Bardet–Biedl syndrome

Author

Bujakowska, Kinga M., Zhang, Qi, Siemiatkowska, Anna M., Liu, Qin, Place, Emily, Falk, Marni J., Consugar, Mark, Lancelot, Marie-Elise, Antonio, Aline, Lonjou, Christine, Carpentier, Wassila, Mohand-Saïd, Saddek, den Hollander, Anneke I., Cremers, Frans P.M., Leroy, Bart P., Gai, Xiaowu, Sahel, José-Alain, van den Born, L. Ingeborgh, Collin, Rob W.J., Zeitz, Christina, Audo, Isabelle, and Pierce, Eric A.

Published
2015
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7. WDR34, a candidate gene for non-syndromic rod-cone dystrophy

Author

Ministère de l’Enseignement supérieur et de la Recherche (France), Fondation de France, Foundation Fighting Blindness, Fondation Voir et Entendre, Agence Nationale de la Recherche (France), National Eye Institute (US), Région Ile-de-France, Association Française contre les Myopathies, Solaguren-Beascoa, María, Bujakowska, Kinga, Méjécase, Cécile, Emmenegger, Lisa, Orhan, Elise, Neuillé, Marion, Mohand-Saïd, Saddek, Condroyer, Christel, Lancelot, Marie-Elise, Michiels, Christelle, Demontant, Vanessa, Antonio, Aline, Letexier, Mélanie, Saraiva, Jean-Paul, Lonjou, Christine, Carpentier, Wassila, Léveillard, Thierry, Pierce, Eric A., Dollfus, Hélène, Sahel, José-Alain, Bhattacharya, Shom Shanker, Audo, Isabelle, Zeitz, Christina, Ministère de l’Enseignement supérieur et de la Recherche (France), Fondation de France, Foundation Fighting Blindness, Fondation Voir et Entendre, Agence Nationale de la Recherche (France), National Eye Institute (US), Région Ile-de-France, Association Française contre les Myopathies, Solaguren-Beascoa, María, Bujakowska, Kinga, Méjécase, Cécile, Emmenegger, Lisa, Orhan, Elise, Neuillé, Marion, Mohand-Saïd, Saddek, Condroyer, Christel, Lancelot, Marie-Elise, Michiels, Christelle, Demontant, Vanessa, Antonio, Aline, Letexier, Mélanie, Saraiva, Jean-Paul, Lonjou, Christine, Carpentier, Wassila, Léveillard, Thierry, Pierce, Eric A., Dollfus, Hélène, Sahel, José-Alain, Bhattacharya, Shom Shanker, Audo, Isabelle, and Zeitz, Christina

Abstract

Rod-cone dystrophy (RCD), also called retinitis pigmentosa, is characterized by rod followed by cone photoreceptor degeneration, leading to gradual visual loss. Mutations in over 65 genes have been associated with non-syndromic RCD explaining 60% to 70% of cases, with novel gene defects possibly accounting for the unsolved cases. Homozygosity mapping and whole-exome sequencing applied to a case of autosomal recessive non-syndromic RCD from a consanguineous union identified a homozygous variant in WDR34. Mutations in WDR34 have been previously associated with severe ciliopathy syndromes possibly associated with a retinal dystrophy. This is the first report of a homozygous mutation in WDR34 associated with non-syndromic RCD.

Published
2021

8. A novel DFNB31 mutation associated with Usher type 2 syndrome showing variable degrees of auditory loss in a consanguineous Portuguese family

Author

Audo, Isabelle, Bujakowska, Kinga, Mohand-Said, Saddek, Tronche, Sophie, Lancelot, Marie-Elise, Antonio, Aline, Germain, Aurore, Lonjou, Christine, Carpentier, Wassila, Sahel, Jose-Alain, Bhattacharya, Shomi, Christina Zeitz, Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Institute of Ophthalmology [London], University College of London [London] (UCL), Plateforme Post-génomique de la Pitié-Salpêtrière (P3S), UMS omique (OMIQUE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Gestionnaire, Hal Sorbonne Université, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
Adult, Male, Genotype, genetic structures, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Molecular Sequence Data, Mutation, Missense, Genes, Recessive, Polymorphism, Single Nucleotide, Severity of Illness Index, Consanguinity, Humans, Age of Onset, Hearing Loss, Oligonucleotide Array Sequence Analysis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Base Sequence, Portugal, Vision Tests, Homozygote, Chromosome Mapping, Membrane Proteins, Middle Aged, Pedigree, [SDV] Life Sciences [q-bio], Phenotype, Female, sense organs, Usher Syndromes, Retinitis Pigmentosa, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract

International audience; PURPOSE:To identify the genetic defect of a consanguineous Portuguese family with rod-cone dystrophy and varying degrees of decreased audition.METHODS:A detailed ophthalmic and auditory examination was performed on a Portuguese patient with severe autosomal recessive rod-cone dystrophy. Known genetic defects were excluded by performing autosomal recessive retinitis pigmentosa (arRP) genotyping microarray analysis and by Sanger sequencing of the coding exons and flanking intronic regions of eyes shut homolog-drosophila (EYS) and chromosome 2 open reading frame 71 (C2orf71). Subsequently, genome-wide homozygosity mapping was performed in DNA samples from available family members using a 700K single nucleotide polymorphism (SNP) microarray. Candidate genes present in the significantly large homozygous regions were screened for mutations using Sanger sequencing.RESULTS:The largest homozygous region (~11 Mb) in the affected family members was mapped to chromosome 9, which harbors deafness, autosomal recessive 31 (DFNB31; a gene previously associated with Usher syndrome). Mutation analysis of DFNB31 in the index patient identified a novel one-base-pair deletion (c.737delC), which is predicted to lead to a truncated protein (p.Pro246HisfsX13) and co-segregated with the disease in the family. Ophthalmic examination of the index patient and the affected siblings showed severe rod-cone dystrophy. Pure tone audiometry revealed a moderate hearing loss in the index patient, whereas the affected siblings were reported with more profound and early onset hearing impairment.CONCLUSIONS:We report a novel truncating mutation in DFNB31 associated with severe rod-cone dystrophy and varying degrees of hearing impairment in a consanguineous family of Portuguese origin. This is the second report of DFNB31 implication in Usher type 2.

Published
2020

9. Combining network-guided GWAS to discover susceptibility mechanisms for breast cancer

Author

Climente-González, Héctor, Lonjou, Christine, Lesueur, Fabienne, collaborators, GENESIS Study, Stoppa-Lyonnet, Dominique, Andrieu, Nadine, and Azencott, Chloé-Agathe

Abstract

Systems biology provides a comprehensive approach to biomarker discovery and biological hypothesis building. Indeed, it allows to jointly consider the statistical association between gene variation and a phenotype, and the biological context of each gene, represented as a network. In this work, we study six network methods which identify subnetworks with high association scores to a phenotype. Specifically, we examine their utility to discover new biomarkers for breast cancer susceptibility by interrogating a genome-wide association study (GWAS) focused on French women with a family history of breast cancer and tested negative for pathogenic variants in BRCA1 and BRCA2 . We perform an in-depth benchmarking of the methods with regards to size of the solution subnetwork, their utility as biomarkers, and the stability and the runtime of the methods. By trading statistical stringency for biological meaningfulness, most network methods give more compelling results than standard SNP- and gene-level analyses, recovering causal subnetworks tightly related to cancer susceptibility. For instance, we show a general alteration of the neighborhood of COPS5 , a gene related to multiple hallmarks of cancer. Importantly, we find a significantly large overlap between the genes in the solution networks and the genes significantly associated in the largest GWAS on susceptibility to breast cancer. Yet, network methods are notably unstable, producing different results when the input data changes slightly. To account for that, we produce a stable consensus subnetwork, formed by the most consistently selected genes. The stable consensus is composed of 68 genes, enriched in known breast cancer susceptibility genes ( BLM , CASP8 , CASP10 , DNAJC1 , FGFR2 , MRPS30 , and SLC4A7 , Fisher’s exact test P-value = 3 × 10 -4 ) and occupying more central positions in the network than average. The network seems organized around CUL3 , encoding an ubiquitin ligase related protein that regulates the protein levels of several genes involved in cancer progression. In conclusion, this article shows the pertinence of network-based analyses to tackle known issues with GWAS, namely lack of statistical power and of interpretable solutions. Project-agnostic implementations of each of the network methods are available at https://github.com/hclimente/gwas-tools to facilitate their application to other GWAS datasets.

Published
2020
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10. Gene‐ and pathway‐level analyses of iCOGS variants highlight novel signaling pathways underlying familial breast cancer susceptibility

Author

Lonjou, Christine, primary, Eon‐Marchais, Séverine, additional, Truong, Thérèse, additional, Dondon, Marie‐Gabrielle, additional, Karimi, Mojgan, additional, Jiao, Yue, additional, Damiola, Francesca, additional, Barjhoux, Laure, additional, Le Gal, Dorothée, additional, Beauvallet, Juana, additional, Mebirouk, Noura, additional, Cavaciuti, Eve, additional, Chiesa, Jean, additional, Floquet, Anne, additional, Audebert‐Bellanger, Séverine, additional, Giraud, Sophie, additional, Frebourg, Thierry, additional, Limacher, Jean‐Marc, additional, Gladieff, Laurence, additional, Mortemousque, Isabelle, additional, Dreyfus, Hélène, additional, Lejeune‐Dumoulin, Sophie, additional, Lasset, Christine, additional, Venat‐Bouvet, Laurence, additional, Bignon, Yves‐Jean, additional, Pujol, Pascal, additional, Maugard, Christine M., additional, Luporsi, Elisabeth, additional, Bonadona, Valérie, additional, Noguès, Catherine, additional, Berthet, Pascaline, additional, Delnatte, Capucine, additional, Gesta, Paul, additional, Lortholary, Alain, additional, Faivre, Laurence, additional, Buecher, Bruno, additional, Caron, Olivier, additional, Gauthier‐Villars, Marion, additional, Coupier, Isabelle, additional, Mazoyer, Sylvie, additional, Monraz, Luis‐Cristobal, additional, Kondratova, Maria, additional, Kuperstein, Inna, additional, Guénel, Pascal, additional, Barillot, Emmanuel, additional, Stoppa‐Lyonnet, Dominique, additional, Andrieu, Nadine, additional, and Lesueur, Fabienne, additional

Published
2021
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11. CRB1 mutations in inherited retinal dystrophies

Author

Bujakowska, Kinga, Audo, Isabelle, Mohand-Saïd, Saddek, Lancelot, Marie-Elise, Antonio, Aline, Germain, Aurore, Léveillard, Thierry, Letexier, Mélanie, Saraiva, Jean-Paul, Lonjou, Christine, Carpentier, Wassila, Sahel, José-Alain, Bhattacharya, Shomi S., and Zeitz, Christina

Published
2012
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12. WDR34 , a candidate gene for non‐syndromic rod‐cone dystrophy

Author

Solaguren‐Beascoa, Maria, primary, Bujakowska, Kinga M., additional, Méjécase, Cécile, additional, Emmenegger, Lisa, additional, Orhan, Elise, additional, Neuillé, Marion, additional, Mohand‐Saïd, Saddek, additional, Condroyer, Christel, additional, Lancelot, Marie‐Elise, additional, Michiels, Christelle, additional, Demontant, Vanessa, additional, Antonio, Aline, additional, Letexier, Mélanie, additional, Saraiva, Jean‐Paul, additional, Lonjou, Christine, additional, Carpentier, Wassila, additional, Léveillard, Thierry, additional, Pierce, Eric A., additional, Dollfus, Hélène, additional, Sahel, José‐Alain, additional, Bhattacharya, Shomi S., additional, Audo, Isabelle, additional, and Zeitz, Christina, additional

Published
2020
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14. Familial breast cancer and DNA repair genes: Insights into known and novel susceptibility genes from the GENESIS study, and implications for multigene panel testing

Author

Girard, Elodie, Eon-Marchais, Séverine, Olaso, François, Renault, Anne, Damiola, Francesca, Dondon, Marie-Gabrielle, Barjhoux, Laure, Goidin, Didier, Meyer, François, Le Gal, Dorothée, Beauvallet, Juana, Mebirouk, Noura, Lonjou, Christine, Coignard, Julie, Marcou, Morgane, Cavaciuti, Eve, Baulard, François, Bihoreau, François, Cohen-Haguenauer, Odile, Leroux, Dominique, Penet, Jean, Fert-Ferrer, Sandra, Colas, Chrystelle, Frebourg, Thierry, Eisinger, François, Adenis, Claude, Fajac, Anne, Gladieff, Laurence, Tinat, Julie, Floquet, Anne, Chiesa, Jean, Giraud, Sophie, Mortemousque, Isabelle, Soubrier, Florent, Audebert-Bellanger, Séverine, Limacher, Jean-Marc, Lasset, Christine, Lejeune-Dumoulin, Sophie, Dreyfus, Catherine, Bignon, Yves-Jean, Longy, Michel, Pujol, Pascal, Venat-Bouvet, Laurence, Bonadona, Valérie, Berthet, Pascaline, Luporsi, Elisabeth, Maugard, Christine, Noguès, Catherine, Delnatte, Capucine, Fricker, Paul, Gesta, Paul, Faivre, Laurence, Lortholary, Alain, Buecher, Bruno, Caron, Olivier, Gauthier-Villars, Marion, Coupier, Isabelle, Servant, Nicolas, Boland, Anne, Mazoyer, Sylvie, Deleuze, Jean-François, Stoppa-Lyonnet, Dominique, Andrieu, Nadine, Lesueur, Fabienne, Université Paris sciences et lettres (PSL), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Life Sciences and Diagnostics Group [Les Ulis, France], Agilent Technologies France, Laboratoire Information, Milieux, Médias, Médiations - EA 3820 (I3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université de Toulon (UTLN), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Traitement Algorithmique et Matériel de la Communication, de l'Information et de la Connaissance (TAMCIC), Ecole Nationale Supérieure des Télécommunications de Bretagne-Centre National de la Recherche Scientifique (CNRS), CRLCC Jean Godinot, Centre Hospitalier de Chambéry (C.H.de Chambéry), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département de Génétique [Institut Curie, Paris] (Unité de Pharmacogénomique), Institut Curie [Paris], Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Claudius Regaud, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département d'oncologie médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Laboratoire de Cytogénétique, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Génétique épidémiologique et moléculaire des pathologies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Génétique Moléculaire et d'Histocompatibilité [Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital pasteur [Colmar], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Sainte Catherine [Avignon], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Département de pathologie, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Dupuytren [CHU Limoges], Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Consultation d'Oncogénétique, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Alexis Vautrin (CAV), Laboratoire de Diagnostic Génétique [CHU Strasbourg], Université de Strasbourg (UNISTRA)-CHU Strasbourg, Laboratoire d'Oncogénétique, CRLCC René Huguenin, CRLCC René Gauducheau, Service d'Oncologie Médicale [Strasbourg] (UNICANCER Centre Paul Strauss), Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Centre Catherine-de-Sienne [Nantes] (CCS), Service de Génétique Oncologique, Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Unité d'Oncogénétique, CRLCC Val d'Aurelle - Paul Lamarque, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), 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), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Grant sponsor: comprehensive cancer center SiRIC, Grant numbers: INCa-DGOS-4654, Grant sponsor: Fondation ARC pour la recherche sur le cancer, Grant numbers: PJA 20151203365, Grant sponsor: France Génomique National infrastructure, Grant numbers: ANR-10-INBS-09, Grant sponsor: Institut National du Cancer (INCa), Grant numbers: b2008-029/LL-LC, Grant sponsor: Ligue Comité de Paris, Grant numbers: RS15/75-78, Grant sponsor: Ligue Nationale Contre le Cancer, Grant numbers: PRE05/DSL PRE07/DSL PRE11/NA., Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Epidémiologie des cancers : Radiocarcinogénèse et effets iatrogènes des traitements, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), E06, Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Plateforme Post-génomique de la Pitié-Salpêtrière (P3S), UMS omique (OMIQUE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CRESS, Université de Franche-Comté (UFC), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de génétique médicale CHU Grenoble Hôpital Couple Enfant, CHU Grenoble, CHU Saint-Antoine [APHP], Génétique du cancer et des maladies neuropsychiatriques (GMFC), Centre oscar lambert, service d'hématologie chu, CHU Tenon [APHP], CRLCC Institut Claudius Regaud, Centre Beninois pour l'Environnement et le développement économique et Social (CEBEDES), Service de Génétique Clinique [CHRU Nïmes], Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Service de Pédiatrie et de Génétique Médicale, Hôpital Jeanne de Flandre [Lille], Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Université Clermont Auvergne (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Jean Perrin, CRLCC Jean Perrin, Institut Bergonié - CRLCC Bordeaux, Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Génétique épidémiologique et structures des populations humaines (Inserm U535), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire de diagnostic génétique, Hôpital Universitaire de Strasbourg, Strasbourg, Centre René Gauducheau, Genetic and Immunology Medical Institute (GIMI), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Fédération Francophone de la Cancérologie Digestive, FFCD, Institut Gustave Roussy (IGR), Service d'oncogénétique, Institut Curie, Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Equipe 6, Université Paris Descartes - Paris 5 (UPD5), Méthodologie statistique et épidémiologie génétique des maladies multifactorielles, Institut National de la Santé et de la Recherche Médicale (INSERM), Section Génétique - Groupe Prédispositions génétiques au cancer, Centre International de Recherche contre le Cancer (CIRC), MINES ParisTech - École nationale supérieure des mines de Paris, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure des Télécommunications de Bretagne, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Lille Nord de France (COMUE)-UNICANCER, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre de recherche en neurosciences de Lyon (CRNL), 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), Andrieu, Nadine, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
Adult, DNA Repair, case-control study, [SDV]Life Sciences [q-bio], Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Risk Assessment, Cancer Genetics and Epigenetics, breast cancer, multigene panel testing, [SDV.CAN] Life Sciences [q-bio]/Cancer, Humans, Genetic Predisposition to Disease, Genetic Testing, Aged, Aged, 80 and over, [SDV.GEN]Life Sciences [q-bio]/Genetics, Siblings, case–control study, Middle Aged, [SDV] Life Sciences [q-bio], variant, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, exome sequencing
Abstract

Pathogenic variants in BRCA1 and BRCA2 only explain the underlying genetic cause of about 10% of hereditary breast and ovarian cancer families. Because of cost‐effectiveness, multigene panel testing is often performed even if the clinical utility of testing most of the genes remains questionable. The purpose of our study was to assess the contribution of rare, deleterious‐predicted variants in DNA repair genes in familial breast cancer (BC) in a well‐characterized and homogeneous population. We analyzed 113 DNA repair genes selected from either an exome sequencing or a candidate gene approach in the GENESIS study, which includes familial BC cases with no BRCA1 or BRCA2 mutation and having a sister with BC (N = 1,207), and general population controls (N = 1,199). Sequencing data were filtered for rare loss‐of‐function variants (LoF) and likely deleterious missense variants (MV). We confirmed associations between LoF and MV in PALB2, ATM and CHEK2 and BC occurrence. We also identified for the first time associations between FANCI, MAST1, POLH and RTEL1 and BC susceptibility. Unlike other associated genes, carriers of an ATM LoF had a significantly higher risk of developing BC than carriers of an ATM MV (ORLoF = 17.4 vs. ORMV = 1.6; p Het = 0.002). Hence, our approach allowed us to specify BC relative risks associated with deleterious‐predicted variants in PALB2, ATM and CHEK2 and to add MAST1, POLH, RTEL1 and FANCI to the list of DNA repair genes possibly involved in BC susceptibility. We also highlight that different types of variants within the same gene can lead to different risk estimates., What's new? Pathogenic variants in BRCA1 and BRCA2 only explain the genetic cause of about 10% of hereditary breast and ovarian cancer families, and the clinical usefulness of testing other genes following the recent introduction of cost‐effective multigene panel sequencing in diagnostics laboratories remains questionable. This large case‐control study describes genetic variation in 113 DNA repair genes and specifies breast cancer relative risks associated with rare deleterious‐predicted variants in PALB2, ATM, and CHEK2. Importantly, different types of variants within the same gene can lead to different risk estimates. The results may help improve risk prediction models and define gene‐specific consensus management guidelines.

Published
2019
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16. Boosting GWAS using biological networks: A study on susceptibility to familial breast cancer.

Author

Climente-González, Héctor, Lonjou, Christine, Lesueur, Fabienne, Stoppa-Lyonnet, Dominique, Andrieu, Nadine, and Azencott, Chloé-Agathe

Subjects
*BRCA genes, *BREAST cancer, *REGULATOR genes, *GENES, *BIOLOGICAL networks, *CANCER genes
Abstract

Genome-wide association studies (GWAS) explore the genetic causes of complex diseases. However, classical approaches ignore the biological context of the genetic variants and genes under study. To address this shortcoming, one can use biological networks, which model functional relationships, to search for functionally related susceptibility loci. Many such network methods exist, each arising from different mathematical frameworks, pre-processing steps, and assumptions about the network properties of the susceptibility mechanism. Unsurprisingly, this results in disparate solutions. To explore how to exploit these heterogeneous approaches, we selected six network methods and applied them to GENESIS, a nationwide French study on familial breast cancer. First, we verified that network methods recovered more interpretable results than a standard GWAS. We addressed the heterogeneity of their solutions by studying their overlap, computing what we called the consensus. The key gene in this consensus solution was COPS5, a gene related to multiple cancer hallmarks. Another issue we observed was that network methods were unstable, selecting very different genes on different subsamples of GENESIS. Therefore, we proposed a stable consensus solution formed by the 68 genes most consistently selected across multiple subsamples. This solution was also enriched in genes known to be associated with breast cancer susceptibility (BLM, CASP8, CASP10, DNAJC1, FGFR2, MRPS30, and SLC4A7, P-value = 3 × 10−4). The most connected gene was CUL3, a regulator of several genes linked to cancer progression. Lastly, we evaluated the biases of each method and the impact of their parameters on the outcome. In general, network methods preferred highly connected genes, even after random rewirings that stripped the connections of any biological meaning. In conclusion, we present the advantages of network-guided GWAS, characterize their shortcomings, and provide strategies to address them. To compute the consensus networks, implementations of all six methods are available at https://github.com/hclimente/gwas-tools. Author summary: Genome-wide association studies (GWAS) scan thousands of genomes to identify variants associated with a complex trait. Over the last 15 years, GWAS have advanced our understanding of the genetics of complex diseases, and in particular of cancers. However, they have led to an apparent paradox: the more we perform such studies, the more it seems that the entire genome is involved in every disease. The omnigenic model offers an appealing explanation: only a limited number of core genes are directly involved in the disease, but gene functions are deeply interrelated, and so many other genes can alter the function of the core genes. These interrelations are often modeled as networks, and multiple algorithms have been proposed to use these networks to identify the subset of core genes involved in a specific trait. This study applies and compares six such network methods on GENESIS, a GWAS dataset for familial breast cancer in the French population. Combining these approaches allows us to identify potentially novel breast cancer susceptibility genes and provides a mechanistic explanation for their role in the development of the disease. We provide ready-to-use implementations of all the examined methods. [ABSTRACT FROM AUTHOR]

Published
2021
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17. WDR34, a candidate gene for non‐syndromic rod‐cone dystrophy.

Author

Solaguren‐Beascoa, Maria, Bujakowska, Kinga M., Méjécase, Cécile, Emmenegger, Lisa, Orhan, Elise, Neuillé, Marion, Mohand‐Saïd, Saddek, Condroyer, Christel, Lancelot, Marie‐Elise, Michiels, Christelle, Demontant, Vanessa, Antonio, Aline, Letexier, Mélanie, Saraiva, Jean‐Paul, Lonjou, Christine, Carpentier, Wassila, Léveillard, Thierry, Pierce, Eric A., Dollfus, Hélène, and Sahel, José‐Alain

Subjects
HOMOZYGOSITY, DYSTROPHY, RETINITIS pigmentosa, RETINAL degeneration, GENES, CILIOPATHY
Abstract

Rod‐cone dystrophy (RCD), also called retinitis pigmentosa, is characterized by rod followed by cone photoreceptor degeneration, leading to gradual visual loss. Mutations in over 65 genes have been associated with non‐syndromic RCD explaining 60% to 70% of cases, with novel gene defects possibly accounting for the unsolved cases. Homozygosity mapping and whole‐exome sequencing applied to a case of autosomal recessive non‐syndromic RCD from a consanguineous union identified a homozygous variant in WDR34. Mutations in WDR34 have been previously associated with severe ciliopathy syndromes possibly associated with a retinal dystrophy. This is the first report of a homozygous mutation in WDR34 associated with non‐syndromic RCD. [ABSTRACT FROM AUTHOR]

Published
2021
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18. Familial breast cancer and DNA repair genes: Insights into known and novel susceptibility genes from the GENESIS study, and implications for multigene panel testing

Author

Girard, Elodie, primary, Eon‐Marchais, Séverine, additional, Olaso, Robert, additional, Renault, Anne‐Laure, additional, Damiola, Francesca, additional, Dondon, Marie‐Gabrielle, additional, Barjhoux, Laure, additional, Goidin, Didier, additional, Meyer, Vincent, additional, Le Gal, Dorothée, additional, Beauvallet, Juana, additional, Mebirouk, Noura, additional, Lonjou, Christine, additional, Coignard, Juliette, additional, Marcou, Morgane, additional, Cavaciuti, Eve, additional, Baulard, Céline, additional, Bihoreau, Marie‐Thérèse, additional, Cohen‐Haguenauer, Odile, additional, Leroux, Dominique, additional, Penet, Clotilde, additional, Fert‐Ferrer, Sandra, additional, Colas, Chrystelle, additional, Frebourg, Thierry, additional, Eisinger, François, additional, Adenis, Claude, additional, Fajac, Anne, additional, Gladieff, Laurence, additional, Tinat, Julie, additional, Floquet, Anne, additional, Chiesa, Jean, additional, Giraud, Sophie, additional, Mortemousque, Isabelle, additional, Soubrier, Florent, additional, Audebert‐Bellanger, Séverine, additional, Limacher, Jean‐Marc, additional, Lasset, Christine, additional, Lejeune‐Dumoulin, Sophie, additional, Dreyfus, Hélène, additional, Bignon, Yves‐Jean, additional, Longy, Michel, additional, Pujol, Pascal, additional, Venat‐Bouvet, Laurence, additional, Bonadona, Valérie, additional, Berthet, Pascaline, additional, Luporsi, Elisabeth, additional, Maugard, Christine M., additional, Noguès, Catherine, additional, Delnatte, Capucine, additional, Fricker, Jean‐Pierre, additional, Gesta, Paul, additional, Faivre, Laurence, additional, Lortholary, Alain, additional, Buecher, Bruno, additional, Caron, Olivier, additional, Gauthier‐Villars, Marion, additional, Coupier, Isabelle, additional, Servant, Nicolas, additional, Boland, Anne, additional, Mazoyer, Sylvie, additional, Deleuze, Jean‐François, additional, Stoppa‐Lyonnet, Dominique, additional, Andrieu, Nadine, additional, and Lesueur, Fabienne, additional

Published
2018
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20. Investigation of DNA repair-related SNPs underlying susceptibility to papillary thyroid carcinoma reveals MGMT as a novel candidate gene in Belarusian children exposed to radiation

Author

Lonjou, Christine, primary, Damiola, Francesca, additional, Moissonnier, Monika, additional, Durand, Geoffroy, additional, Malakhova, Irina, additional, Masyakin, Vladimir, additional, Le Calvez-Kelm, Florence, additional, Cardis, Elisabeth, additional, Byrnes, Graham, additional, Kesminiene, Ausrele, additional, and Lesueur, Fabienne, additional

Published
2017
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21. A novel DFNB31 mutation associated with Usher type 2 syndrome showing variable degrees of auditory loss in a consanguineous Portuguese family

Author

Audo, Isabelle, Bujakowska, Kinga, Tronche, Sophie, Lonjou, Christine, Carpentier, Wassila, Bhattacharya, Shom Shanker, and Zeitz, Christina

Subjects
genetic structures, Membrane proteins, sense organs, DFNB31 protein
Abstract

Purpose: To identify the genetic defect of a consanguineous Portuguese family with rod-cone dystrophy and varying degrees of decreased audition. Methods: A detailed ophthalmic and auditory examination was performed on a Portuguese patient with severe autosomal recessive rod-cone dystrophy. Known genetic defects were excluded by performing autosomal recessive retinitis pigmentosa (arRP) genotyping microarray analysis and by Sanger sequencing of the coding exons and flanking intronic regions of eyes shut homolog-drosophila (EYS) and chromosome 2 open reading frame 71 (C2orf71). Subsequently, genome-wide homozygosity mapping was performed in DNA samples from available family members using a 700K single nucleotide polymorphism (SNP) microarray. Candidate genes present in the significantly large homozygous regions were screened for mutations using Sanger sequencing. Results: The largest homozygous region (~11 Mb) in the affected family members was mapped to chromosome 9, which harbors deafness, autosomal recessive 31 (DFNB31; a gene previously associated with Usher syndrome). Mutation analysis of DFNB31 in the index patient identified a novel one-base-pair deletion (c.737delC), which is predicted to lead to a truncated protein (p.Pro246HisfsX13) and co-segregated with the disease in the family. Ophthalmic examination of the index patient and the affected siblings showed severe rod-cone dystrophy. Pure tone audiometry revealed a moderate hearing loss in the index patient, whereas the affected siblings were reported with more profound and early onset hearing impairment. Conclusions: We report a novel truncating mutation in DFNB31 associated with severe rod-cone dystrophy and varying degrees of hearing impairment in a consanguineous family of Portuguese origin. This is the second report of DFNB31 implication in Usher type 2. © 2011 Molecular Vision., The project was financially supported by the Foundation Fighting Blindness (I.A. FFB Grant N°: CD-CL-0808–0466-CHNO and the CIC503 recognized as an FFB center, FFB Grant No: C-CMM-0907–0428-INSERM04), Agence Nationale de la Recherche (S.S.B.), Foundation Voir et Entendre (C.Z.), Ville de Paris and region Ile de France.

Published
2011

22. Models including pathological and radiomic features vs clinical models in predicting outcome of patients with metastatic non-small cell lung cancer treated with immunotherapy.

Author

Captier, Nicolas, Lerousseau, Marvin, Orlhac, Fanny, Hovhannisyan, Narinée, Luporsi, Marie, Lagha, Sarah, Tedesco, Anne-Sophie, Salamoun Feghali, Paulette, Lonjou, Christine, Ramtohul, Toulsie, Beaulaton, Clément, Brisse, Hervé, Vincent-Salomon, Anne, Walter, Thomas, Buvat, Irène, Girard, Nicolas, and Barillot, Emmanuel

Published
2023
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23. Mutations in IFT172 cause isolated retinal degeneration and Bardet–Biedl syndrome

Author

Bujakowska, Kinga M., primary, Zhang, Qi, additional, Siemiatkowska, Anna M., additional, Liu, Qin, additional, Place, Emily, additional, Falk, Marni J., additional, Consugar, Mark, additional, Lancelot, Marie-Elise, additional, Antonio, Aline, additional, Lonjou, Christine, additional, Carpentier, Wassila, additional, Mohand-Saïd, Saddek, additional, den Hollander, Anneke I., additional, Cremers, Frans P.M., additional, Leroy, Bart P., additional, Gai, Xiaowu, additional, Sahel, José-Alain, additional, van den Born, L. Ingeborgh, additional, Collin, Rob W.J., additional, Zeitz, Christina, additional, Audo, Isabelle, additional, and Pierce, Eric A., additional

Published
2014
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24. EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension

Author

Eyries, Mélanie, primary, Montani, David, additional, Girerd, Barbara, additional, Perret, Claire, additional, Leroy, Anne, additional, Lonjou, Christine, additional, Chelghoum, Nadjim, additional, Coulet, Florence, additional, Bonnet, Damien, additional, Dorfmüller, Peter, additional, Fadel, Elie, additional, Sitbon, Olivier, additional, Simonneau, Gérald, additional, Tregouët, David-Alexandre, additional, Humbert, Marc, additional, and Soubrier, Florent, additional

Published
2013
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25. Positive selection of protective variants for type 2 diabetes from the Neolithic onward: a case study in Central Asia

Author

Ségurel, Laure, primary, Austerlitz, Frederic, additional, Toupance, Bruno, additional, Gautier, Mathieu, additional, Kelley, Joanna L, additional, Pasquet, Patrick, additional, Lonjou, Christine, additional, Georges, Myriam, additional, Voisin, Sarah, additional, Cruaud, Corinne, additional, Couloux, Arnaud, additional, Hegay, Tatyana, additional, Aldashev, Almaz, additional, Vitalis, Renaud, additional, and Heyer, Evelyne, additional

Published
2013
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26. CRB1 mutations in inherited retinal dystrophies

Author

Bujakowska, Kinga, primary, Audo, Isabelle, additional, Mohand-Saïd, Saddek, additional, Lancelot, Marie-Elise, additional, Antonio, Aline, additional, Germain, Aurore, additional, Léveillard, Thierry, additional, Letexier, Mélanie, additional, Saraiva, Jean-Paul, additional, Lonjou, Christine, additional, Carpentier, Wassila, additional, Sahel, José-Alain, additional, Bhattacharya, Shomi S., additional, and Zeitz, Christina, additional

Published
2011
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28. A European study of HLA-B in Stevens–Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs

Author

Lonjou, Christine, primary, Borot, Nicolas, additional, Sekula, Peggy, additional, Ledger, Neil, additional, Thomas, Laure, additional, Halevy, Sima, additional, Naldi, Luigi, additional, Bouwes-Bavinck, Jan-Nico, additional, Sidoroff, Alexis, additional, de Toma, Claudia, additional, Schumacher, Martin, additional, Roujeau, Jean-Claude, additional, Hovnanian, Alain, additional, and Mockenhaupt, Maja, additional

Published
2008
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30. EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension.

Author

Eyries, Mélanie, Montani, David, Girerd, Barbara, Perret, Claire, Leroy, Anne, Lonjou, Christine, Chelghoum, Nadjim, Coulet, Florence, Bonnet, Damien, Dorfmüller, Peter, Fadel, Elie, Sitbon, Olivier, Simonneau, Gérald, Tregouët, David-Alexandre, Humbert, Marc, and Soubrier, Florent

Subjects
GENETIC mutation, CELL proliferation, PULMONARY hypertension, HETEROZYGOSITY, ATRIAL septal defects, GENETICS
Abstract

Pulmonary veno-occlusive disease (PVOD) is a rare and devastating cause of pulmonary hypertension that is characterized histologically by widespread fibrous intimal proliferation of septal veins and preseptal venules and is frequently associated with pulmonary capillary dilatation and proliferation. PVOD is categorized into a separate pulmonary arterial hypertension-related group in the current classification of pulmonary hypertension. PVOD presents either sporadically or as familial cases with a seemingly recessive mode of transmission. Using whole-exome sequencing, we detected recessive mutations in EIF2AK4 (also called GCN2) that cosegregated with PVOD in all 13 families studied. We also found biallelic EIF2AK4 mutations in 5 of 20 histologically confirmed sporadic cases of PVOD. All mutations, either in a homozygous or compound-heterozygous state, disrupted the function of the gene. These findings point to EIF2AK4 as the major gene that is linked to PVOD development and contribute toward an understanding of the complex genetic architecture of pulmonary hypertension. [ABSTRACT FROM AUTHOR]

Published
2014
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32. HLA ABDR HAPLOTYPE FREQUENCIES IN FRANCE—IMPLICATIONS FOR RECRUITMENT OF POTENTIAL BONE MARROW DONORS

Author

LONJOU, CHRISTINE, CLAYTON, JOHN, CAMBON-THOMSEN, ANNE, and RAFFOUX, COLETTE

Abstract

We have undertaken a study of the haplotypes among French potential bone marrow donors in order to define the geographical regions of France with the maximum of polymorphism and also to develop a strategy for optimal donor recruitment. A maximum likelihood estimator was used to calculate haplotype frequencies and their support limits for each region and for the whole of France. The observed differences between the regions were statistically significant. For each region, the minimum number of haplotypes necessary to explain 50 of the total frequency was calculated and compared with the equivalent values, and confidence intervals, obtained by repeated random samplings from the overall file. This approach shows that some regions (e.g., Provence) appear to be richer in terms of the numbers of haplotypes observed, and others (e.g., Bretagne) poorer. In the latter case however, the frequencies of the most common haplotypes are greater. The haplotype frequencies of the whole sample were used to calculate the probability of finding a match for the next potential recipient for given sizes of the donor file, assuming random selection of donors. They were also used to calculate expected numbers of the major phenotypes, assuming Hardy-Weinberg equilibrium, and these were compared with those observed in the real data file. In this way, a large number of under-represented and nonrepresented phenotypes were identified. For each of these phenotypes, the most probable haplotypes and the regions in which these have the greatest frequencies have been identified. A search for donors with such particular phenotypes would be much more fruitful if directed towards these regions.

Published
1995

33. Familial breast cancer and DNA repair genes: Insights into known and novel susceptibility genes from the GENESIS study, and implications for multigene panel testing.

Author

Girard E, Eon-Marchais S, Olaso R, Renault AL, Damiola F, Dondon MG, Barjhoux L, Goidin D, Meyer V, Le Gal D, Beauvallet J, Mebirouk N, Lonjou C, Coignard J, Marcou M, Cavaciuti E, Baulard C, Bihoreau MT, Cohen-Haguenauer O, Leroux D, Penet C, Fert-Ferrer S, Colas C, Frebourg T, Eisinger F, Adenis C, Fajac A, Gladieff L, Tinat J, Floquet A, Chiesa J, Giraud S, Mortemousque I, Soubrier F, Audebert-Bellanger S, Limacher JM, Lasset C, Lejeune-Dumoulin S, Dreyfus H, Bignon YJ, Longy M, Pujol P, Venat-Bouvet L, Bonadona V, Berthet P, Luporsi E, Maugard CM, Noguès C, Delnatte C, Fricker JP, Gesta P, Faivre L, Lortholary A, Buecher B, Caron O, Gauthier-Villars M, Coupier I, Servant N, Boland A, Mazoyer S, Deleuze JF, Stoppa-Lyonnet D, Andrieu N, and Lesueur F

Subjects
Adult, Aged, Aged, 80 and over, Breast Neoplasms diagnosis, Case-Control Studies, Female, Humans, Middle Aged, Risk Assessment methods, Siblings, Breast Neoplasms genetics, DNA Repair genetics, Genetic Predisposition to Disease, Genetic Testing methods
Abstract

Pathogenic variants in BRCA1 and BRCA2 only explain the underlying genetic cause of about 10% of hereditary breast and ovarian cancer families. Because of cost-effectiveness, multigene panel testing is often performed even if the clinical utility of testing most of the genes remains questionable. The purpose of our study was to assess the contribution of rare, deleterious-predicted variants in DNA repair genes in familial breast cancer (BC) in a well-characterized and homogeneous population. We analyzed 113 DNA repair genes selected from either an exome sequencing or a candidate gene approach in the GENESIS study, which includes familial BC cases with no BRCA1 or BRCA2 mutation and having a sister with BC (N = 1,207), and general population controls (N = 1,199). Sequencing data were filtered for rare loss-of-function variants (LoF) and likely deleterious missense variants (MV). We confirmed associations between LoF and MV in PALB2, ATM and CHEK2 and BC occurrence. We also identified for the first time associations between FANCI, MAST1, POLH and RTEL1 and BC susceptibility. Unlike other associated genes, carriers of an ATM LoF had a significantly higher risk of developing BC than carriers of an ATM MV (OR LoF = 17.4 vs. OR MV = 1.6; p Het = 0.002). Hence, our approach allowed us to specify BC relative risks associated with deleterious-predicted variants in PALB2, ATM and CHEK2 and to add MAST1, POLH, RTEL1 and FANCI to the list of DNA repair genes possibly involved in BC susceptibility. We also highlight that different types of variants within the same gene can lead to different risk estimates., (© 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Published
2019
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