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

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...

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Detalles Bibliográficos
Autores: Urreizti, Roser, Cueto Gonzalez, Anna Maria, Franco Valls, Héctor, Mort Farre, Sílvia, Roca Ayats, Neus, Ponomarenko, Julia, Cozzuto, Luca, Company, Carlos, Bosio, Mattia, Ossowski, Stephan, Montfort Roca, Magda, Hecht, Jochen, Tizzano Ferrari, Eduardo, Cormand Rifà, Bru, Vilageliu i Arqués, Lluïsa, Opitz, John M., Neri, Giovanni, Grinberg Vaisman, Daniel Raúl, Balcells Comas, Susana
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/119645
Acceso en línea:https://hdl.handle.net/2445/119645
Access Level:acceso abierto
Palabra clave:Neurobiologia del desenvolupament
Biologia molecular
Developmental neurobiology
Molecular biology
Descripción
Sumario: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.

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