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Exome sequencing identifies the first genetic determinants of sirenomelia in humans.
Lecoquierre, François; Brehin, Anne-Claire; Coutant, Sophie; Coursimault, Juliette; Bazin, Anne; Finck, Wilfrid; Benoist, Guillaume; Begorre, Marianne; Beneteau, Claire; Cailliez, Daniel; Chenal, Pierre; De Jong, Mirjam; Degré, Sophie; Devisme, Louise; Francannet, Christine; Gérard, Bénédicte; Jeanne, Corinne; Joubert, Madeleine; Journel, Hubert; Laurichesse Delmas, Hélène; Layet, Valérie; Liquier, Alain; Mangione, Raphaele; Patrier, Sophie; Pelluard, Fanny; Petit, Florence; Tillouche, Nadia; van Ravenswaaij-Arts, Conny; Frebourg, Thierry; Saugier-Veber, Pascale; Gruchy, Nicolas; Nicolas, Gaël; Gerard, Marion.
Afiliación
  • Lecoquierre F; Department of Genetics and Reference Center for Developmental Disorders, Normandy Center for Genomic and Personalized Medicine, Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Rouen, France.
  • Brehin AC; Department of Genetics and Reference Center for Developmental Disorders, Normandy Center for Genomic and Personalized Medicine, Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Rouen, France.
  • Coutant S; Department of Foetopathology, CHU Rouen, Rouen, France.
  • Coursimault J; Department of Genetics and Reference Center for Developmental Disorders, Normandy Center for Genomic and Personalized Medicine, Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Rouen, France.
  • Bazin A; Department of Genetics and Reference Center for Developmental Disorders, Normandy Center for Genomic and Personalized Medicine, Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Rouen, France.
  • Finck W; Département de Génétique et de Biologie Spécialisée, Laboratoire Cerba, Saint Ouen l'Aumone, France.
  • Benoist G; Unité de Foetopathologie, Laboratoire d'anatomie et cytologie pathologique, CHU Clermont Ferrand, Clermont-Ferrand, France.
  • Begorre M; Service de gynécologie-obstétrique et médecine de la reproduction, Centre Hospitalier Universitaire de Caen, Universite de Caen Normandie, Caen, Basse-Normandie, France.
  • Beneteau C; Department of Obstetrics, CHU Côte de Nacre, Caen, France.
  • Cailliez D; Department of Clinical genetics, CHU Hôpital mère et enfant, Nantes, France.
  • Chenal P; Department of Foetopathology, Hopital Monod, Le Havre, France.
  • De Jong M; Department of Foetopathology, Hopital Monod, Le Havre, France.
  • Degré S; Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
  • Devisme L; CPDPN, Hopital Monod, Le Havre, France.
  • Francannet C; Institut de Pathologie, CHU Lille, Lille, France.
  • Gérard B; Centre de référence des anomalies malformatives, Service de génétique médicale, CHU Clermont-Ferrand, Clermont-Ferrand, France.
  • Jeanne C; Centre d'Etude des Malformations Congénitales, CEMC-Auvergne, CHU Clermont-Ferrand, Clermont-Ferrand, France.
  • Joubert M; Department of Genetics, CHU de Strasbourg, Hôpital Civil, Strasbourg, France.
  • Journel H; Department of Foetopathology, Centre François Baclesse, CHU Côte de Nacre, Caen, France.
  • Laurichesse Delmas H; Department of Foetopathology, CHU Hôtel Dieu, Nantes, France.
  • Layet V; Department of Clinical ge netics, CH Vannes, Vannes, France.
  • Liquier A; Centre d'Etude des Malformations Congénitales, CEMC-Auvergne, CHU Clermont-Ferrand, Clermont-Ferrand, France.
  • Mangione R; Unité de Médecine Fœtale, Service de gynécologie-obstétrique, CHU Clermont-Ferrand, Clermont-Ferrand, France.
  • Patrier S; Department of Clinical Genetics, Hopital Monod, Le Havre, France.
  • Pelluard F; CPDPN, Hôpital Bagatelle, Talence, France.
  • Petit F; Departement of Radiology, Polyclinique Bordeaux Nord-Aquitaine, Bordeaux, France.
  • Tillouche N; Department of Foetopathology, CHU Rouen, Rouen, France.
  • van Ravenswaaij-Arts C; Service d'Anatomie-Cytologie Pathologique, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
  • Frebourg T; INSERM UMR1053, Bordeaux Research in Translational Oncology, BaRITOn, Université de Bordeaux, Bordeaux, France.
  • Saugier-Veber P; Clinique de Génétique "Guy Fontaine"-Centre de référence CLAD, Hôpital Jeanne de Flandre, CHU Lille, Lille, France.
  • Gruchy N; Pôle Femme-Mère-Nouveau-né, Centre Hospitalier de Valenciennes, Valenciennes, France.
  • Nicolas G; Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
  • Gerard M; Department of Genetics and Reference Center for Developmental Disorders, Normandy Center for Genomic and Personalized Medicine, Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Rouen, France.
Hum Mutat ; 41(5): 926-933, 2020 05.
Article en En | MEDLINE | ID: mdl-32058622
Sirenomelia is a rare severe malformation sequence of unknown cause characterized by fused legs and severe visceral abnormalities. We present a series of nine families including two rare familial aggregations of sirenomelia investigated by a trio-based exome sequencing strategy. This approach identified CDX2 variants in the two familial aggregations, both fitting an autosomal dominant pattern of inheritance with variable expressivity. CDX2 is a major regulator of caudal development in vertebrate and mouse heterozygotes are a previously described model of sirenomelia. Remarkably, the p.(Arg237His) variant has already been reported in a patient with persistent cloaca. Analysis of the sporadic cases revealed six additional candidate variants including a de novo frameshift variant in the genetically constrained NKD1 gene, encoding a known interactor of CDX2. We provide the first insights for a genetic contribution in human sirenomelia and highlight the role of Cdx and Wnt signaling pathways in the development of this disorder.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Ectromelia / Estudios de Asociación Genética / Secuenciación del Exoma Tipo de estudio: Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Hum Mutat Asunto de la revista: GENETICA MEDICA Año: 2020 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Ectromelia / Estudios de Asociación Genética / Secuenciación del Exoma Tipo de estudio: Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Hum Mutat Asunto de la revista: GENETICA MEDICA Año: 2020 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos