title: MSX2 Gene Duplication in a Patient with Eye Development Defects.
abstract: BACKGROUND
  MSX2 mutations are a very rare cause of craniosynostosis. Gain-of-function mutations may lead to the Boston-type craniosynostosis with limb defects and refraction errors, whereas loss-of-function mutations causes primary osseous defects such as enlarged parietal foramina.
  
  
  METHODS
  Herein we report the case of a child with bicoronal synostosis and cutaneous syndactylies, who presented iridal and chorioretinal colobomas. Due to the craniofacial features that were prominent in the clinical picture, the genes involved in craniosynostosis were explored.
  
  
  RESULTS
  The patient disclosed an intragenic duplication of the entire MSX2 gene whereas no mutation was identified in any major genes known to be involved in craniosynostosis.
  
  
  CONCLUSIONS
  This is the first report of an eye development defect due to an increase in the MSX2 copy number in a human being. The implication of this gene in eye development has already been shown in several animal models. Indeed, overexpression of the Msx2 gene in a mouse model resulted also in optic nerve aplasia and microphthalmia. This report expands the phenotypic spectrum of the MSX2 mutations impacting early ocular development knowledge.
authors.affiliation: a Centre de référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), Hôpital Civil , Strasbourg , France .
authors.forename: Julie
authors.initials: J
authors.lastname: Plaisancié
authors.affiliation: b Service de Biochimie et Biologie Moléculaire, Hôpital Lariboisière , Paris , France .
authors.forename: Corinne
authors.initials: C
authors.lastname: Collet
authors.affiliation: a Centre de référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), Hôpital Civil , Strasbourg , France .
authors.forename: Valerie
authors.initials: V
authors.lastname: Pelletier
authors.affiliation: a Centre de référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), Hôpital Civil , Strasbourg , France .
authors.forename: Yaumara
authors.initials: Y
authors.lastname: Perdomo
authors.affiliation: a Centre de référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), Hôpital Civil , Strasbourg , France .
authors.forename: Fouzia
authors.initials: F
authors.lastname: Studer
authors.affiliation: c Service de Génétique Médicale, Hôpital de Hautepierre , Strasbourg , France .
authors.forename: Mélanie
authors.initials: M
authors.lastname: Fradin
authors.affiliation: c Service de Génétique Médicale, Hôpital de Hautepierre , Strasbourg , France .
authors.forename: Elise
authors.initials: E
authors.lastname: Schaefer
authors.affiliation: d Service d'Ophtalmologie, Nouvel Hôpital Civil , Strasbourg , France .
authors.forename: Claude
authors.initials: C
authors.lastname: Speeg-Schatz
authors.affiliation: e Reference Centre for Orodental Manifestations of Rare Diseases, Pôle de Médecine et Chirurgie Bucco-Dentaires, Hôpitaux Universitaires de Strasbourg , Strasbourg , France .
authors.forename: Agnès
authors.initials: A
authors.lastname: Bloch-Zupan
authors.affiliation: f Laboratoire de Cytogénétique , Hôpital de Hautepierre , Strasbourg , France , and.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Flori
authors.affiliation: a Centre de référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), Hôpital Civil , Strasbourg , France .|c Service de Génétique Médicale, Hôpital de Hautepierre , Strasbourg , France .|g Laboratoire de Génétique Médicale , INSERM U1112 , Strasbourg , France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
mesh_terms: D002675:Child, Preschool; D003103:Coloboma / Q000235:genetics*; D003398:Craniosynostoses / Q000235:genetics*; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D005260:Female; D020440:Gene Duplication; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D016133:Polymerase Chain Reaction; D047928:Premature Birth
chemical_list: D018398:Homeodomain Proteins; C084119:MSX2 protein
keywords: Boston-type craniosynostosis; MSX2; coloboma; eye development