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

Mouna Barat-Houari 1 Bruno Dumont 2 Aurelie J Fabre 2 Frédéric Tm Them 2 Yves Alembik 3 Jean-Luc Alessandri 4 Jeanne Amiel 5 Séverine Audebert Clarisse Baumann-Morel Patricia Blanchet 2 Eric Bieth 6 Marie Brechard Tiffany Busa 7 Patrick Calvas 8 Yline Capri 9 Francois Cartault 10 Nicolas Chassaing 8 Vidrica Ciorca Christine Coubes 2 Albert David 11 Anne-Lise Delezoide 12 Delphine Dupin-Deguine 13 Salima El Chehadeh Laurence Faivre 14 Fabienne Giuliano 15 Alice Goldenberg 16 Bertrand Isidor 17 Marie-Line Jacquemont 4 Sophie Julia 18 Josseline Kaplan 19 Didier Lacombe 20 Marine Lebrun Sandrine Marlin 21 Dominique Martin-Coignard 22 Jelena Martinovic 23 Alice Masurel 24 Judith Melki 25 Monique Mozelle-Nivoix Karine Nguyen 26 Sylvie Odent 27 Nicole Philip 28 Lucile Pinson 2 Ghislaine Plessis 29 Chloé Quélin 30 Elise Shaeffer Sabine Sigaudy 7 Christel Thauvin 24 Marianne Till 31 Renaud Touraine 32 Jacqueline Vigneron 33 Geneviève Baujat 5 Valérie Cormier-Daire 34 Martine Le Merrer David Geneviève 1 Isabelle Touitou 35, 2
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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Submitted on : Tuesday, December 8, 2015 - 11:46:14 AM
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Mouna Barat-Houari, Bruno Dumont, Aurelie J Fabre, Frédéric Tm Them, Yves Alembik, et al.. The expanding spectrum of COL2A1 gene variants IN 136 patients with a skeletal dysplasia phenotype. European Journal of Human Genetics, Nature Publishing Group, 2016, 24 (7), pp.992-1000. ⟨10.1038/ejhg.2015.250⟩. ⟨hal-01239808⟩

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