title: Large deletions encompassing the TCOF1 and CAMK2A genes are responsible for Treacher Collins syndrome with intellectual disability.
abstract: Mandibulofacial dysostosis is part of a clinically and genetically heterogeneous group of disorders of craniofacial development, which lead to malar and mandibular hypoplasia. Treacher Collins syndrome is the major cause of mandibulofacial dysostosis and is due to mutations in the TCOF1 gene. Usually patients with Treacher Collins syndrome do not present with intellectual disability. Recently, the EFTUD2 gene was identified in patients with mandibulofacial dysostosis associated with microcephaly, intellectual disability and esophageal atresia. We report on two patients presenting with mandibulofacial dysostosis characteristic of Treacher Collins syndrome, but associated with unexpected intellectual disability, due to a large deletion encompassing several genes including the TCOF1 gene. We discuss the involvement of the other deleted genes such as CAMK2A or SLC6A7 in the cognitive development delay of the patients reported, and we propose the systematic investigation for 5q32 deletion when intellectual disability is associated with Treacher Collins syndrome.
authors.affiliation: Département de Génétique Médicale, CHRU Montpellier, Faculté de Médecine de Montpellier-Mimes, Université Montpellier 1, Montpellier, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Vincent
authors.affiliation: Service de Biologie Moléculaire, Hôpital Lariboisière, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Collet
authors.affiliation: Département de Génétique Médicale, Hôpital Robert Debré, Paris, France, Université Denis Diderot Sorbonne-Paris, INSERM U676, Département de Génétique, Sart Tilman University Hospital, Liège, Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.affiliation: Service de Génétique Médicale, CHRU de Nancy-Brabois, Nancy, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Lambert
authors.affiliation: Service de Chirurgie Plastique Infantile, CHRU Montpellier, Montpellier, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Herlin
authors.affiliation: Service d'Oto-rhino-laryngologie, CHRU Montpellier, Montpellier, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Blanchet
authors.affiliation: Département de Génétique Médicale, CHRU Montpellier, Faculté de Médecine de Montpellier-Mimes, Université Montpellier 1, Montpellier, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Sanchez
authors.affiliation: Département de Génétique Médicale, Hôpital Robert Debré, Paris, France, Université Denis Diderot Sorbonne-Paris, INSERM U676, Département de Génétique, Sart Tilman University Hospital, Liège, Belgium.
authors.forename: Séverine
authors.initials: S
authors.lastname: Drunat
authors.affiliation: Service de Génétique Médicale, CHRU de Nancy-Brabois, Nancy, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Vigneron
authors.affiliation: Service de Biologie Moléculaire, Hôpital Lariboisière, Paris, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Laplanche
authors.affiliation: Département de Génétique Médicale, CHRU Montpellier, Faculté de Médecine de Montpellier-Mimes, Université Montpellier 1, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Puechberty
authors.affiliation: Département de Génétique Médicale, CHRU Montpellier, Faculté de Médecine de Montpellier-Mimes, Université Montpellier 1, Montpellier, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarda
authors.affiliation: Département de Génétique Médicale, CHRU Montpellier, Faculté de Médecine de Montpellier-Mimes, Université Montpellier 1, Montpellier, France.
authors.forename: David
authors.initials: D
authors.lastname: Geneviève
mesh_terms: D000293:Adolescent; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics*; D002648:Child; D005260:Female; D017353:Gene Deletion; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008342:Mandibulofacial Dysostosis / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; D010750:Phosphoproteins; C105442:TCOF1 protein, human; C517657:CAMK2A protein, human; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2