Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/113221
Title: Mutations in JMJD1C are involved in Rett syndrome and intellectual disability
Author: Sáez, Mauricio A.
Fernández-Rodríguez, Juana
Moutinho, Cátia
Sanchez-Mut, Jose Vicente
Gómez, Antonio
Vidal, Enrique
Petazzi, Paolo
Szczesna, Karolina
Lopez-Serra, Paula
Lucariello, Mario
Lorden, Patricia
Delgado-Morales, Raul
de la Caridad, Olga J.
Huertas, Dori
Gelpí Buchaca, Josep Lluís
Orozco López, Modesto
López-Dóriga Guerra, Adriana
Milà i Recasens, Montserrat
Perez-Jurado, Luís A.
Pineda, Mercedes
Armstrong i Morón, Judith
Lázaro García, Conxi
Esteller, Manel
Keywords: Síndrome de Rett
Discapacitats mentals
Autisme
Trastorns de l'espectre autista
Mutació (Biologia)
Rett syndrome
People with mental disabilities
Autism
Autism spectrum disorders
Mutation (Biology)
Issue Date: Apr-2016
Publisher: American College of Medical Genetics and Genomics
Abstract: Purpose: autism spectrum disorders are associated with defects in social response and communication that often occur in the context of intellectual disability. Rett syndrome is one example in which epilepsy, motor impairment, and motor disturbance may co-occur. Mutations in histone demethylases are known to occur in several of these syndromes. Herein, we aimed to identify whether mutations in the candidate histone demethylase JMJD1C (jumonji domain containing 1C) are implicated in these disorders. Methods: we performed the mutational and functional analysis of JMJD1C in 215 cases of autism spectrum disorders, intellectual disability, and Rett syndrome without a known genetic defect. Results: we found seven JMJD1C variants that were not present in any control sample (~ 6,000) and caused an amino acid change involving a different functional group. From these, two de novo JMJD1C germline mutations were identified in a case of Rett syndrome and in a patient with intellectual disability. The functional study of the JMJD1C mutant Rett syndrome patient demonstrated that the altered protein had abnormal subcellular localization, diminished activity to demethylate the DNA damage-response protein MDC1, and reduced binding to MECP2. We confirmed that JMJD1C protein is widely expressed in brain regions and that its depletion compromises dendritic activity. Conclusions: our findings indicate that mutations in JMJD1C contribute to the development of Rett syndrome and intellectual disability.
Note: Reproducció del document publicat a: https://doi.org/10.1038/gim.2015.100
It is part of: Genetics in Medicine, 2016, vol. 18, num. 4, p. 378-385
Related resource: https://doi.org/10.1038/gim.2015.100
URI: http://hdl.handle.net/2445/113221
ISSN: 1098-3600
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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