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2016-04

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cc-by-nc-nd (c) Sáez, Mauricio A. et al., 2016
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/113221

Mutations in JMJD1C are involved in Rett syndrome and intellectual disability

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https://doi.org/10.1038/gim.2015.100

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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.

Matèries

Síndrome de Rett, Discapacitats mentals, Autisme, Trastorns de l'espectre autista, Mutació (Biologia)

Matèries (anglès)

Rett syndrome, People with mental disabilities, Autism, Autism spectrum disorders, Mutation (Biology)

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Articles publicats en revistes (Ciències Fisiològiques)
<b>Publicacions de projectes de recerca finançats per la UE</b>
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citació

SÁEZ, Mauricio a., FERNÁNDEZ RODRÍGUEZ, Juana, MOUTINHO, Cátia, SANCHEZ-MUT, Jose vicente, GÓMEZ, Antonio, VIDAL, Enrique, PETAZZI, Paolo, SZCZESNA, Karolina, LÓPEZ SERRA, Paula, LUCARIELLO, Mario, LORDEN, Patricia, DELGADO-MORALES, Raul, CARIDAD, Olga j. de la, HUERTAS, Dori, GELPÍ BUCHACA, Josep lluís, OROZCO LÓPEZ, Modesto, LÓPEZ DÓRIGA GUERRA, Adriana, MILÀ I RECASENS, Montserrat, PÉREZ JURADO, Luis a., PINEDA, Mercedes, ARMSTRONG I MORÓN, Judith, LÁZARO GARCÍA, Conxi, ESTELLER, Manel. Mutations in JMJD1C are involved in Rett syndrome and intellectual disability. _Genetics in Medicine_. 2016. Vol. 18, núm. 4, pàgs. 378-385. [consulta: 23 de gener de 2026]. ISSN: 1098-3600. [Disponible a: https://hdl.handle.net/2445/113221]

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