The expanding spectrum of COL2A1 gene variants IN 136 patients with a skeletal dysplasia phenotype

Mouna Barat-Houari; Bruno Dumont; Aurelie J Fabre; Frédéric Tm Them; Yves Alembik; Jean-Luc Alessandri; Jeanne Amiel; Séverine Audebert; Clarisse Baumann-Morel; Patricia Blanchet; Eric Bieth; Marie Brechard; Tiffany Busa; Patrick Calvas; Yline Capri; Francois Cartault; Nicolas Chassaing; Vidrica Ciorca; Christine Coubes; Albert David; Anne-Lise Delezoide; Delphine Dupin-Deguine; Salima El Chehadeh; Laurence Faivre; Fabienne Giuliano; Alice Goldenberg; Bertrand Isidor; Marie-Line Jacquemont; Sophie Julia; Josseline Kaplan; Didier Lacombe; Marine Lebrun; Sandrine Marlin; Dominique Martin-Coignard; Jelena Martinovic; Alice Masurel; Judith Melki; Monique Mozelle-Nivoix; Karine Nguyen; Sylvie Odent; Nicole Philip; Lucile Pinson; Ghislaine Plessis; Chloé Quélin; Elise Shaeffer; Sabine Sigaudy; Christel Thauvin; Marianne Till; Renaud Touraine; Jacqueline Vigneron; Geneviève Baujat; Valérie Cormier-Daire; Martine Le Merrer; David Geneviève; Isabelle Touitou

doi:10.1038/ejhg.2015.250

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The expanding spectrum of COL2A1 gene variants IN 136 patients with a skeletal dysplasia phenotype

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The expanding spectrum of COL2A1 gene variants IN 136 patients with a skeletal dysplasia phenotype

Mouna Barat-Houari, Bruno Dumont, Aurelie J Fabre, Frédéric Tm Them, Yves Alembik, Jean-Luc Alessandri, Jeanne Amiel, Séverine Audebert, Clarisse Baumann-Morel, Patricia Blanchet, …

European Journal of Human Genetics, Vol.24(7), pp.992-1000

07/2016

DOI: https://doi.org/10.1038/ejhg.2015.250

PMCID: PMC5070901

PMID: 26626311

Abstract

Heterozygous COL2A1 variants cause a wide spectrum of skeletal dysplasia termed type II collagenopathies. We assessed the impact of this gene in our French series. A decision tree was applied to select 136 probands (71 Stickler cases, 21 Spondyloepiphyseal dysplasia congenita cases, 11 Kniest dysplasia cases, and 34 other dysplasia cases) before molecular diagnosis by Sanger sequencing. We identified 66 different variants among the 71 positive patients. Among those patients, 18 belonged to multiplex families and 53 were sporadic. Most variants (38/44, 86%) were located in the triple helical domain of the collagen chain and glycine substitutions were mainly observed in severe phenotypes, whereas arginine to cysteine changes were more often encountered in moderate phenotypes. This series of skeletal dysplasia is one of the largest reported so far, adding 44 novel variants (15%) to published data. We have confirmed that about half of our Stickler patients (46%) carried a COL2A1 variant, and that the molecular spectrum was different across the phenotypes. To further address the question of genotype-phenotype correlation, we plan to screen our patients for other candidate genes using a targeted next-generation sequencing approach.European Journal of Human Genetics advance online publication, 2 December 2015; doi:10.1038/ejhg.2015.250

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Title: The expanding spectrum of COL2A1 gene variants IN 136 patients with a skeletal dysplasia phenotype
Creators - without role: Mouna Barat-Houari - Université de Montpellier, Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Bruno Dumont - Centre Hospitalier Régional Universitaire [Montpellier]
Aurelie J Fabre - Centre Hospitalier Régional Universitaire [Montpellier]
Frédéric Tm Them - Centre Hospitalier Régional Universitaire [Montpellier]
Yves Alembik - Hôpital d'Hautepierre
Jean-Luc Alessandri - Centre Hospitalier Universitaire de La Réunion
Jeanne Amiel - Inserm
Séverine Audebert - Centre Hospitalier Régional Universitaire de Brest
Clarisse Baumann-Morel - Hôpital Robert-Debré
Patricia Blanchet - Centre Hospitalier Régional Universitaire [Montpellier]
Eric Bieth - Hôpital Purpan
Marie Brechard - Hôpital Saint Joseph
Tiffany Busa - Hôpital de la Timone
Patrick Calvas - Hôpital Purpan
Yline Capri - Hôpital Robert-Debré
Francois Cartault - Centre Hospitalier Universitaire de La Réunion
Nicolas Chassaing - Hôpital Purpan
Vidrica Ciorca - Centre Hospitalier Régional et Universitaire de Nancy
Christine Coubes - Centre Hospitalier Régional Universitaire [Montpellier]
Albert David - Génétique Médicale & Génomique Fonctionelle
Anne-Lise Delezoide - Service de Biologie du Développement
Delphine Dupin-Deguine - Hôpital Purpan
Salima El Chehadeh - Hôpital d'Enfants
Laurence Faivre - Hôpital d'Enfants
Fabienne Giuliano - Centre Hospitalier Universitaire de Nice
Alice Goldenberg - Hôpital Charles-Nicolle
Bertrand Isidor - Génétique Médicale & Génomique Fonctionelle
Marie-Line Jacquemont - Centre Hospitalier Universitaire de La Réunion
Sophie Julia - Hôpital Purpan
Josseline Kaplan - Université Paris Cité
Didier Lacombe - Hôpital Pellegrin
Marine Lebrun - Hôpital Nord
Sandrine Marlin - Hôpital Armand-Trousseau
Dominique Martin-Coignard - Service de génétique
Jelena Martinovic - Hôpital Antoine-Béclère
Alice Masurel - Hôpital d'Enfants
Judith Melki - Bicêtre Hospital
Monique Mozelle-Nivoix
Karine Nguyen - Hôpital d'Enfants
Sylvie Odent - Laboratoire de Génétique Cellulaire
Nicole Philip - Hôpital de la Timone
Lucile Pinson - Centre Hospitalier Régional Universitaire [Montpellier]
Ghislaine Plessis - Centre Hospitalier Universitaire de Caen
Chloé Quélin - Centre Hospitalier Universitaire de Rennes
Elise Shaeffer - Hôpital d'Hautepierre
Sabine Sigaudy - Hôpital de la Timone
Christel Thauvin - Hôpital d'Enfants
Marianne Till - Service de cytogénétique constitutionnelle
Renaud Touraine - Hôpital Nord
Jacqueline Vigneron - Centre Hospitalier Régional Universitaire de Nancy
Geneviève Baujat - Inserm
Valérie Cormier-Daire - Inserm
Martine Le Merrer - Inserm
David Geneviève - Université de Montpellier, Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Isabelle Touitou - Université de Montpellier, Institut de Génétique Humaine - IGH
Publication Details: European Journal of Human Genetics, Vol.24(7), pp.992-1000
Identifiers: 9963610409311
Academic Unit: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB; Institut de Génétique Humaine - IGH
Language: English
Resource Type: Journal article
Local Fields: hal-01239808