A de novo nonsense mutation in MAGEL2 in a patient initially diagnosed as Opitz-C: similarities between Schaaf-Yang and Opitz-C syndromes

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  • dc.contributor.author Urreizti, Roserca
  • dc.contributor.author Cueto González, Anna Maríaca
  • dc.contributor.author Franco Valls, Héctorca
  • dc.contributor.author Mort Farre, Sílviaca
  • dc.contributor.author Roca Ayats, Neusca
  • dc.contributor.author Ponomarenko, Juliaca
  • dc.contributor.author Cozzuto, Lucaca
  • dc.contributor.author Company, Carlosca
  • dc.contributor.author Bosio, Mattiaca
  • dc.contributor.author Ossowski, Stephanca
  • dc.contributor.author Montfort, Magdaca
  • dc.contributor.author Hecht, Jochenca
  • dc.contributor.author Tizzano, Eduardo F.ca
  • dc.contributor.author Cormand, Bruca
  • dc.contributor.author Vilageliu, Lluïsaca
  • dc.contributor.author Opitz, John M.ca
  • dc.contributor.author Neri, Giovannica
  • dc.contributor.author Grinberg, Danielca
  • dc.contributor.author Balcells, Susanaca
  • dc.date.accessioned 2018-07-23T07:58:28Z
  • dc.date.available 2018-07-23T07:58:28Z
  • dc.date.issued 2017
  • dc.description.abstract Opitz trigonocephaly C syndrome (OTCS) is a rare genetic disorder characterized by craniofacial anomalies, variable intellectual and psychomotor disability, and variable cardiac defects with a high mortality rate. Different patterns of inheritance and genetic heterogeneity are known in this syndrome. Whole exome and genome sequencing of a 19-year-old girl (P7), initially diagnosed with OTCS, revealed a de novo nonsense mutation, p.Q638*, in the MAGEL2 gene. MAGEL2 is an imprinted, maternally silenced, gene located at 15q11-13, within the Prader-Willi region. Patient P7 carried the mutation in the paternal chromosome. Recently, mutations in MAGEL2 have been described in Schaaf-Yang syndrome (SHFYNG) and in severe arthrogryposis. Patient P7 bears resemblances with SHFYNG cases but has other findings not described in this syndrome and common in OTCS. We sequenced MAGEL2 in nine additional OTCS patients and no mutations were found. This study provides the first clear molecular genetic basis for an OTCS case, indicates that there is overlap between OTCS and SHFYNG syndromes, and confirms that OTCS is genetically heterogeneous. Genes encoding MAGEL2 partners, either in the retrograde transport or in the ubiquitination-deubiquitination complexes, are promising candidates as OTCS disease-causing genes.
  • dc.description.sponsorship Funding was from Associació Síndrome Opitz C, Terrassa, Spain; Spanish Ministerio de Economía y Competitividad (SAF2014-56562-R; FECYT, crowdfunding PRECIPITA); Catalan Government (2014SGR932) and from CIBERER (U720). We acknowledge support of the Spanish Ministry of Economy and Competitiveness, 'Centro de Excelencia Severo Ochoa 2013-2017'.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Urreizti R, Cueto-Gonzalez AM, Franco-Valls H, Mort-Farre S, Roca-Ayats N, Ponomarenko J et al. A De Novo Nonsense Mutation in MAGEL2 in a Patient Initially Diagnosed as Opitz-C: Similarities Between Schaaf-Yang and Opitz-C Syndromes. Sci Rep. 2017 Mar 10;7:44138. DOI: 10.1038/srep44138
  • dc.identifier.doi http://dx.doi.org/10.1038/srep44138
  • dc.identifier.issn 2045-2322
  • dc.identifier.uri http://hdl.handle.net/10230/35222
  • dc.language.iso eng
  • dc.publisher Nature Publishing Groupca
  • dc.relation.ispartof Scientific Reports. 2017 Mar 10;7:44138
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2014-56562-R
  • dc.rights © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Molecular medicine
  • dc.subject.keyword Magel2
  • dc.subject.keyword Schaaf-yang syndrome
  • dc.subject.keyword Opitz trigonocephaly C syndrome
  • dc.title A de novo nonsense mutation in MAGEL2 in a patient initially diagnosed as Opitz-C: similarities between Schaaf-Yang and Opitz-C syndromesca
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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