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Artículo

Identification of a somatic mutation in the RHEB gene through high depth and ultra-high depth next generation sequencing in a patient with Hemimegalencephaly and drug resistant Epilepsy

Salinas Calderon, Valeria MacarenaIcon ; Vega, Liliana Patricia; Piccirilli, María Victoria; Chicco, Carla; Ciraolo, Carlos; Christiansen, Silvia Beatriz; Consalvo, Damian; Perez Maturo, JosefinaIcon ; Medina, Nancy; González Morón, DoloresIcon ; Novaro, VirginiaIcon ; Perrone, Maria CeciliaIcon ; García, María del Carmen; Agosta, Guillermo; Silva, WalterIcon ; Kauffman, Marcelo AndresIcon
Fecha de publicación: 11/2019
Editorial: Elsevier Science
Revista: European Journal Of Medical Genetics
ISSN: 1769-7212
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Otras Ciencias de la Salud

Resumen

Malformations of cortical development are a frequent cause of drug-resistant Epilepsy and developmental delay. Hemimegalencephaly is a Malformation of cortical development characterized by enlargement of all or a part of one cerebral hemisphere. Germline and somatic mutation in genes belonging to the Mammalian Target of Rapamycin (mTOR) pathway has been identified in patients suffering from epilepsy secondary to Hemimegalencephaly and focal cortical dysplasia. We present here a patient suffering from severe neonatal Epilepsy since 3 h of life secondary to Hemimegalencephaly, requiring an anatomic hemispherectomy surgical procedure for seizure control, where by means of next-generation sequencing at an ultra-high depth coverage, we were able to identify a novel somatic mutation in the RHEB gene (NM_005614: c.119A > T: p. Glu40Val). The histopathological diagnosis was Cortical Dysplasia type IIB determined by the presence of dysmorphic neurons of variable size with nuclear alteration and balloon cells in the context of Hemimegalencephaly, which are similar to that have been demonstrated in hyperactivating RHEB models. This is the first report of a somatic mutation in RHEB gene in a patient suffering from Epilepsy secondary to Hemimegalencephaly. It highlights different current topics in the fields of genetics of Malformations of cortical development: a-somatic mosaicism is not uncommon in these neurodevelopmental disorders; b-the molecular diagnostic approach should involve the use of state-of-the-art methods and the sampling of different tissues; c-new findings might facilitate therapeutics discoveries while providing an improved understanding of normal brain development.
Palabras clave: DRUG RESISTANT EPILEPSY , HEMIMEGALENCEPHALY , RHEB GENE , SOMATIC MUTATION
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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)
Identificadores
URI: http://hdl.handle.net/11336/94104
URL: https://www.sciencedirect.com/science/article/pii/S1769721218305718
DOI: http://dx.doi.org/10.1016/j.ejmg.2018.11.005
Colecciones
Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos(IIMT)
Articulos de INSTITUTO DE INVESTIGACIONES EN MEDICINA TRASLACIONAL
Citación
Salinas Calderon, Valeria Macarena; Vega, Liliana Patricia; Piccirilli, María Victoria; Chicco, Carla; Ciraolo, Carlos; et al.; Identification of a somatic mutation in the RHEB gene through high depth and ultra-high depth next generation sequencing in a patient with Hemimegalencephaly and drug resistant Epilepsy; Elsevier Science; European Journal Of Medical Genetics; 62; 11; 11-2019; 1-5; 103571
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