title: Autosomal recessive variations of TBX6, from congenital scoliosis to spondylocostal dysostosis.
abstract: Proximal 16p11.2 microdeletions are recurrent microdeletions with an overall prevalence of 0.03%. In patients with segmentation defects of the vertebra (SDV), a burden of this microdeletion was observed with TBX6 as a candidate gene for SDV. In a published cohort of patients with congenital scoliosis (CS), TBX6 haploinsufficiency was compound heterozygous with a common haplotype. Besides, a single three-generation family with spondylocostal dysostosis (SCD) was reported with a heterozygous stop-loss of TBX6. These observations questioned both on the inheritance mode and on the variable expressivity associated with TBX6-associated SDV. Based on a national recruitment of 56 patients with SDV, we describe four patients with variable SDV ranging from CS to SCD associated with biallelic variations of TBX6. Two patients with CS were carrying a proximal 16p11.2 microdeletion associated with the previously reported haplotype. One patient with extensive SDV was carrying a proximal 16p11.2 microdeletion associated with a TBX6 rare missense change. One patient with a clinical diagnosis of SCD was compound heterozygous for two TBX6 rare missense changes. The three rare variants were affecting the chromatin-binding domain. Our data illustrate the variable expressivity of recessive TBX6 ranging from CS to SCD.
authors.affiliation: GAD EA4271 «Génétique des Anomalies du Développement» (GAD), Université de Bourgogne, Dijon, France.|Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Est, FHU-TRANSLAD, CHU Dijon, Dijon, France.
authors.forename: M
authors.initials: M
authors.lastname: Lefebvre
authors.affiliation: GAD EA4271 «Génétique des Anomalies du Développement» (GAD), Université de Bourgogne, Dijon, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Duffourd
authors.affiliation: GAD EA4271 «Génétique des Anomalies du Développement» (GAD), Université de Bourgogne, Dijon, France.
authors.forename: T
authors.initials: T
authors.lastname: Jouan
authors.affiliation: GAD EA4271 «Génétique des Anomalies du Développement» (GAD), Université de Bourgogne, Dijon, France.
authors.forename: C
authors.initials: C
authors.lastname: Poe
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Est, FHU-TRANSLAD, CHU Dijon, Dijon, France.
authors.forename: N
authors.initials: N
authors.lastname: Jean-Marçais
authors.affiliation: Département de Génétique, Hôpital Robert Debré, APHP, Paris, France.
authors.forename: A
authors.identifier: http://orcid.org/0000-0003-4819-0264
authors.initials: A
authors.lastname: Verloes
authors.affiliation: GAD EA4271 «Génétique des Anomalies du Développement» (GAD), Université de Bourgogne, Dijon, France.
authors.forename: J
authors.initials: J
authors.lastname: St-Onge
authors.affiliation: GAD EA4271 «Génétique des Anomalies du Développement» (GAD), Université de Bourgogne, Dijon, France.
authors.forename: J-B
authors.initials: JB
authors.lastname: Riviere
authors.affiliation: Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHRU, Lille, France.
authors.forename: F
authors.initials: F
authors.lastname: Petit
authors.affiliation: Service de Génétique Clinique, Hôpital Sart Tilman, Liège, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Pierquin
authors.affiliation: Service de génétique clinique, CLAD Nord de France, CHU Amiens, Amiens, France.
authors.forename: B
authors.initials: B
authors.lastname: Demeer
authors.affiliation: Service de Cytogénétique, Plateau technique de Biologie, CHU Dijon, Dijon, France.
authors.forename: P
authors.initials: P
authors.lastname: Callier
authors.affiliation: GAD EA4271 «Génétique des Anomalies du Développement» (GAD), Université de Bourgogne, Dijon, France.|Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Est, FHU-TRANSLAD, CHU Dijon, Dijon, France.
authors.forename: C
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.affiliation: GAD EA4271 «Génétique des Anomalies du Développement» (GAD), Université de Bourgogne, Dijon, France.|Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Est, FHU-TRANSLAD, CHU Dijon, Dijon, France.
authors.forename: L
authors.initials: L
authors.lastname: Faivre
authors.affiliation: GAD EA4271 «Génétique des Anomalies du Développement» (GAD), Université de Bourgogne, Dijon, France.|Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'Est, FHU-TRANSLAD, CHU Dijon, Dijon, France.
authors.forename: J
authors.identifier: http://orcid.org/0000-0001-9271-3961
authors.initials: J
authors.lastname: Thevenon
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006548:Hernia, Diaphragmatic / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D012600:Scoliosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D013131:Spine / Q000000981:diagnostic imaging / Q000503:physiopathology; D020825:T-Box Domain Proteins / Q000235:genetics*
chemical_list: D020825:T-Box Domain Proteins; C491182:TBX6 protein, human
keywords: 16p11.2 microdeletion; TBX6; congenital scoliosis; spondylocostal dysostosis