Phenotypic spectrum and genomics of undiagnosed arthrogryposis multiplex congenita

Annie Laquerriere; Dana Jaber; Emanuela Abiusi; Jerome Maluenda; Dan Mejlachowicz; Alexandre Vivanti; Klaus Dieterich; Radka Stoeva; Loic Quevarec; Flora Nolent; Valerie Biancalana; Philippe Latour; Damien Sternberg; Yline Capri; Alain Verloes; Bettina Bessieres; Laurence Loeuillet; Tania Attie-Bitach; Jelena Martinovic; Sophie Blesson; Florence Petit; Claire Beneteau; Sandra Whalen; Florent Marguet; Jerome Bouligand; Delphine Heron; Geraldine Viot; Jeanne Amiel; Daniel Amram; Celine Bellesme; Martine Bucourt; Laurence Faivre; Pierre-Simon Jouk; Suonavy Khung; Sabine Sigaudy; Anne-Lise Delezoide; Alice Goldenberg; Marie-Line Jacquemont; Laetitia Lambert; Valerie Layet; Stanislas Lyonnet; Arnold Munnich; Lionel Van Maldergem; Juliette Piard; Fabien Guimiot; Pierre Landrieu; Pascaline Letard; Fanny Pelluard; Laurence Perrin; Marie-Helene Saint-Frison; Haluk Topaloglu; Laetitia Trestard; Catherine Vincent-Delorme; Helge Amthor; Christine Barnerias; Alexandra Benachi; Eric Bieth; Elise Boucher; Valerie Cormier-Daire; Andree Delahaye-Duriez; Isabelle Desguerre; Bruno Eymard; Christine Francannet; Sarah Grotto; Didier Lacombe; Fanny Laffargue; Marine Legendre; Dominique Martin-Coignard; Andre Megarbane; Sandra Mercier; Mathilde Nizon; Luc Rigonnot; Fabienne Prieur; Chloe Quelin; Hanitra Ranjatoelina-Randrianaivo; Nicoletta Resta; Annick Toutain; Helene Verhelst; Marie Vincent; Estelle Colin; Catherine Fallet-Bianco; Michele Granier; Romulus Grigorescu; Julien Saada; Marie Gonzales; Anne Guiochon-Mantel; Jean-Louis Bessereau; Marcel Tawk; Ivo Gut; Cyril Gitiaux; Judith Melki

doi:10.1136/jmedgenet-2020-107595

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Phenotypic spectrum and genomics of undiagnosed arthrogryposis multiplex congenita

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Phenotypic spectrum and genomics of undiagnosed arthrogryposis multiplex congenita

Annie Laquerriere, Dana Jaber, Emanuela Abiusi, Jerome Maluenda, Dan Mejlachowicz, Alexandre Vivanti, Klaus Dieterich, Radka Stoeva, Loic Quevarec, Flora Nolent, …

Journal of medical genetics, Vol.59(6), pp.559-567

01/06/2022

DOI: https://doi.org/10.1136/jmedgenet-2020-107595

PMID: 33820833

Résumé

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Background Arthrogryposis multiplex congenita (AMC) is characterised by congenital joint contractures in two or more body areas. AMC exhibits wide phenotypic and genetic heterogeneity. Our goals were to improve the genetic diagnosis rates of AMC, to evaluate the added value of whole exome sequencing (WES) compared with targeted exome sequencing (TES) and to identify new genes in 315 unrelated undiagnosed AMC families. Methods Several genomic approaches were used including genetic mapping of disease loci in multiplex or consanguineous families, TES then WES. Sanger sequencing was performed to identify or validate variants. Results We achieved disease gene identification in 52.7% of AMC index patients including nine recently identified genes (CNTNAP1, MAGEL2, ADGRG6, ADCY6, GLDN, LGI4, LMOD3, UNC50 and SCN1A). Moreover, we identified pathogenic variants in ASXL3 and STAC3 expanding the phenotypes associated with these genes. The most frequent cause of AMC was a primary involvement of skeletal muscle (40%) followed by brain (22%). The most frequent mode of inheritance is autosomal recessive (66.3% of patients). In sporadic patients born to non-consanguineous parents (n=60), de novo dominant autosomal or X linked variants were observed in 30 of them (50%). Conclusion New genes recently identified in AMC represent 21% of causing genes in our cohort. A high proportion of de novo variants were observed indicating that this mechanism plays a prominent part in this developmental disease. Our data showed the added value of WES when compared with TES due to the larger clinical spectrum of some disease genes than initially described and the identification of novel genes.

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Titre: Phenotypic spectrum and genomics of undiagnosed arthrogryposis multiplex congenita
Créateurs - sans rôle: Annie Laquerriere - Normandie Univ, UNIROUEN, INSERM U1245, Rouen, France
Dana Jaber - Univ Paris Saclay, INSERM, UMR 1195, Le Kremlin Bicetre, France
Emanuela Abiusi - Univ Paris Saclay, INSERM, UMR 1195, Le Kremlin Bicetre, France
Jerome Maluenda - Univ Paris Saclay, INSERM, UMR 1195, Le Kremlin Bicetre, France
Dan Mejlachowicz - Univ Paris Saclay, INSERM, UMR 1195, Le Kremlin Bicetre, France
Alexandre Vivanti - Univ Paris Saclay, INSERM, UMR 1195, Le Kremlin Bicetre, France
Klaus Dieterich - Inserm
Radka Stoeva - Univ Paris Saclay, INSERM, UMR 1195, Le Kremlin Bicetre, France
Loic Quevarec - Univ Paris Saclay, INSERM, UMR 1195, Le Kremlin Bicetre, France
Flora Nolent - Univ Paris Saclay, INSERM, UMR 1195, Le Kremlin Bicetre, France
Valerie Biancalana - CHRU, Lab Diagnost Genet, Strasbourg, France
Philippe Latour - Hosp Civils Lyon, Ctr Biol Est, Bron, France
Damien Sternberg - Sorbonne Univ, Serv Biochim Metabol, Paris, France
Yline Capri - Assistance Publique – Hôpitaux de Paris
Alain Verloes - Assistance Publique – Hôpitaux de Paris
Bettina Bessieres - Assistance Publique – Hôpitaux de Paris
Laurence Loeuillet - Assistance Publique – Hôpitaux de Paris
Tania Attie-Bitach - Assistance Publique – Hôpitaux de Paris
Jelena Martinovic - Univ Paris Saclay, INSERM, UMR 1195, Le Kremlin Bicetre, France
Sophie Blesson - Centre Hospitalier Universitaire de Tours
Florence Petit - CHU Lille, Serv Genet Clin Guy Fontaine, Lille, France
Claire Beneteau - Nantes Université
Sandra Whalen - Sorbonne Univ, UF Genet Clin, Hop Armand Trousseau, Paris, France
Florent Marguet - Normandie Univ, UNIROUEN, INSERM U1245, Rouen, France
Jerome Bouligand - Univ Paris Saclay, Lab Genet Mol Pharmacogenet & Hormonol, Hop Bicetre, AP HP, Le Kremlin Bicetre, France
Delphine Heron - Assistance Publique – Hôpitaux de Paris
Geraldine Viot - Clin Muette, Unite Genet, Paris, France
Jeanne Amiel - Assistance Publique – Hôpitaux de Paris
Daniel Amram - Ctr Hosp Intercommunal Creteil, Unite Genet Clin, Creteil, France
Celine Bellesme - Assistance Publique – Hôpitaux de Paris
Martine Bucourt - Hop Jean Verdier, AP HP, Serv Histol Embryol & Cytogenet, Bondy, France
Laurence Faivre - CHU Dijon, Ctr Genet, Dijon, France
Pierre-Simon Jouk - Univ Grenoble Alpes, CHU Grenoble Alpes, INSERM, U1209, Grenoble, France
Suonavy Khung - Hop Univ Robert Debre, INSERM, Unite Fonct & Foetopathol, UMR 1141, Paris, France
Sabine Sigaudy - Hop Timone Enfant, Dept Med Genet, Marseille, France
Anne-Lise Delezoide - Hop Univ Robert Debre, INSERM, Unite Fonct & Foetopathol, UMR 1141, Paris, France
Alice Goldenberg - Inserm
Marie-Line Jacquemont - CHU Reunion, UF Genet Med, Site GHSR, St Pierre, Reunion, France
Laetitia Lambert - CHRU Nancy, Serv Genet Clin, Nancy, France
Valerie Layet - Grp Hosp Havre, Consultat Genet, Le Havre, France
Stanislas Lyonnet - Univ Paris, Imagine Inst, INSERM UMR 1163, Paris, France
Arnold Munnich - Univ Paris, Imagine Inst, INSERM UMR 1163, Paris, France
Lionel Van Maldergem - Univ Franche Comte, Ctr Genet Humaine, Besancon, France
Juliette Piard - Univ Franche Comte, Ctr Genet Humaine, Besancon, France
Fabien Guimiot - Hop Univ Robert Debre, INSERM, Unite Fonct & Foetopathol, UMR 1141, Paris, France
Pierre Landrieu - Assistance Publique – Hôpitaux de Paris
Pascaline Letard - Assistance Publique – Hôpitaux de Paris
Fanny Pelluard - INSERM, UMR U 1053, Bordeaux, France
Laurence Perrin - Assistance Publique – Hôpitaux de Paris
Marie-Helene Saint-Frison - Hop Univ Robert Debre, INSERM, Unite Fonct & Foetopathol, UMR 1141, Paris, France
Haluk Topaloglu - Yeditepe University
Laetitia Trestard - Hop Belvedere, Serv Pediat, Rouen, France
Catherine Vincent-Delorme - CHU Lille, Serv Genet Clin Guy Fontaine, Lille, France
Helge Amthor - Univ Hosp Raymond Poincare, Neuromusc Reference Ctr, Dept Pediat, Garches, France
Christine Barnerias - Hop Necker Enfants Malad, CR Neuromusc Necker, Serv Neuropediat, Paris, France
Alexandra Benachi - Univ Paris Saclay, INSERM, UMR 1195, Le Kremlin Bicetre, France
Eric Bieth - Hop Purpan, Serv Genet Med, Toulouse, France
Elise Boucher - Univ Franche Comte, Ctr Genet Humaine, Besancon, France
Valerie Cormier-Daire - Hop Necker Enfants Malad, AP HP, Serv Genet Clin, Ctr Reference Malad Osseuses Constitut, Paris, France
Andree Delahaye-Duriez - Hop Jean Verdier, AP HP, Serv Histol Embryol & Cytogenet, Bondy, France
Isabelle Desguerre - Hop Necker Enfants Malad, CR Neuromusc Necker, Serv Neuropediat, Paris, France
Bruno Eymard - Sorbonne Univ, GH Pitie Salpetriere, Paris, France
Christine Francannet - CHU Clermont Ferrand, Serv Genet Med, Clermont Ferrand, France
Sarah Grotto - Assistance Publique – Hôpitaux de Paris
Didier Lacombe - CHU Bordeaux, Hop Pellegrin, Serv Genet Med, Bordeaux, France
Fanny Laffargue - CHU Clermont Ferrand, Serv Genet Med, Clermont Ferrand, France
Marine Legendre - CHU Bordeaux, Hop Pellegrin, Serv Genet Med, Bordeaux, France
Dominique Martin-Coignard - Le Mans Hosp, Dept Med Genet, Le Mans, France
Andre Megarbane - Lebanese Amer Univ, Dept Human Genet, Gilbert & Rose Marie Ghagoury Sch Med, Byblos, Lebanon
Sandra Mercier - Nantes Université
Mathilde Nizon - Nantes Université
Luc Rigonnot - Ctr Hosp Sud Francilien, Serv Gynecol Obstet, Corbeil Essonnes, France
Fabienne Prieur - CHU St Etienne, Serv Genet Clin, St Etienne, France
Chloe Quelin - Centre Hospitalier Universitaire de Rennes
Hanitra Ranjatoelina-Randrianaivo - CHU Reunion, UF Genet Med, Site GHSR, St Pierre, Reunion, France
Nicoletta Resta - Univ Bari Aldo Moro, Med Genet, Dept Biomed Sci & Human Oncol DIMO, Bari, Italy
Annick Toutain - CHU Tours, Serv Genet, Tours, France
Helene Verhelst - Ghent University
Marie Vincent - Nantes Université
Estelle Colin - Centre Hospitalier Universitaire d'Angers
Catherine Fallet-Bianco - Univ Montreal, CHU St Justine, Serv Pathol, Montreal, PQ, Canada
Michele Granier - Ctr Hosp Sud Francilien, Neonatol & Neonatal Intens Care Unit, Corbeil Essonnes, France
Romulus Grigorescu - CHU Paris Est, Hop Enfants Armand Trousseau, Dept Genet & Embryol Med, Unite Genet Dev Foetal, Paris, France
Julien Saada - Hop Antoine Beclere, AP HP, Serv Gynecol Obstet, Clamart, France
Marie Gonzales - Hop Necker Enfants Malad, AP HP, Serv Histol Embryol Cytogenet, Unite Embryofoetopathol, Paris, France
Anne Guiochon-Mantel - Univ Paris Saclay, Lab Genet Mol Pharmacogenet & Hormonol, Hop Bicetre, AP HP, Le Kremlin Bicetre, France
Jean-Louis Bessereau - Univ Lyon, CNRS UMR 5310, INSERM U 1217, Inst NeuroMyoGene, Lyon, France
Marcel Tawk - Univ Paris Saclay, INSERM, UMR 1195, Le Kremlin Bicetre, France
Ivo Gut - Barcelona Inst Sci & Technol BIST, Ctr Genom Regulat CRG, CNAG CRG, Barcelona, Spain
Cyril Gitiaux - Univ Paris, Ctr Reference Malad Neuromusc, Unite Neurophysiol Clin, Hop Necker Enfants Malad,AP HP, Paris, France
Judith Melki - Univ Paris Saclay, INSERM, UMR 1195, Le Kremlin Bicetre, France
Détails de publication: Journal of medical genetics, Vol.59(6), pp.559-567
Éditeur: Bmj Publishing Group
Nombre de pages: 9
Note de subvention: DAJ1891 / Association Francaise contre les Myopathies Agence de Biomedecine Alliance Arthrogrypose AOM10181 / French Ministry of Health Institut National de la Sante et de la Recherche Medicale (Inserm)
Identifiants: 99158808709311
Unité académique: Physiologie et Médecine Expérimentale du coeur et des muscles - PhyMedExp
Langue: English
Type de ressource: Journal article