Researchers Claim to Have Uncovered a Cause of Autism and Intellectual Disabilities

The term intellectual disability covers a large number of clinical entities, some with known cause and others of uncertain origin. For example Down syndrome is due to an extra copy of chromosome 21 and Rett syndrome is in part caused by a mutation in the control switch gene called MeCP2.

In other cases the mechanisms by which they are produced are not clearly identified. It is the case of most of those disorders classified under the large umbrella of autism. A study published in the journal Genetics in Medicine by Manel Esteller, director of the Program Epigenetics and Cancer Biology (PEBC) of the Bellvitge Biomedical Research Institute (IDIBELL), ICREA researcher and Professor of Genetics at the University of Barcelona, reports researchers have discovered a mechanism that identifies a cause of intellectual disabilities in these puzzling cases.

“We have analyzed the genome of 215 patients with mental retardation, autism or Rett syndrome, in which they had not found any genetic alteration in the genes classically associated with these clinical conditions, to see if we could find a molecular cause. This process has allowed us to detect a new mutated gene that could be causing these disorders.” Explained Manel Esteller.

This image shows a double helix DNA strand.
Researchers claim to have discovered a mechanism that identifies a cause of intellectual disabilities This image is for illustrative purposes only.

“Specifically, the identified gene is called JMJD1C (Jumonji Domain Containing 1C) and is an epigenetic gene which its normal function is to control the activity of other genes. Only a small percentage of mental retardation of unknown origin is due to mutation of this gene. This finding suggests that many genes with low frequency disturbance are responsible for cases with unknown cause. They have demonstrated that this gene joins the MeCP2 gene so it could also contribute to cases of atypical Rett Syndrome,” says Esteller.

About this Genetics research

Funding: This study has been possible thanks to the support received from the European Union, the Catalan and Spanish associations of Rett syndrome, a campaign of crowdfunding in Verkami and Foundations Daniel Bravo and Finestrelles. Demonstrating the involvement of civil society in research.

Source: IDIBELL
Image Credit: The image is in the public domain
Original Research: Full open access research for “Mutations in JMJD1C are involved in Rett syndrome and intellectual disability” by Mauricio A. Sáez, Juana Fernández-Rodríguez, Catia Moutinho, Jose V. Sanchez-Mut, Antonio Gomez, Enrique Vidal, Paolo Petazzi, Karolina Szczesna, Paula Lopez-Serra, Mario Lucariello, Patricia Lorden, Raul Delgado-Morales, Olga J. de la Caridad, Dori Huertas, Josep L. Gelpí, Modesto Orozco, Adriana López-Doriga, Montserrat Milà, Luís A. Perez-Jurado, Mercedes Pineda, Judith Armstrong, Conxi Lázaro and Manel Esteller in Genetics in Medicine. Published only July 16 2015 doi:10.1038/gim.2015.100


Abstract

Mutations in JMJD1C are involved in Rett syndrome and intellectual disability

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.

“Mutations in JMJD1C are involved in Rett syndrome and intellectual disability” by Mauricio A. Sáez, Juana Fernández-Rodríguez, Catia Moutinho, Jose V. Sanchez-Mut, Antonio Gomez, Enrique Vidal, Paolo Petazzi, Karolina Szczesna, Paula Lopez-Serra, Mario Lucariello, Patricia Lorden, Raul Delgado-Morales, Olga J. de la Caridad, Dori Huertas, Josep L. Gelpí, Modesto Orozco, Adriana López-Doriga, Montserrat Milà, Luís A. Perez-Jurado, Mercedes Pineda, Judith Armstrong, Conxi Lázaro and Manel Esteller in Genetics in Medicine. Published only July 16 2015 doi:10.1038/gim.2015.100

Feel free to share this neuroscience news.
Join our Newsletter
I agree to have my personal information transferred to AWeber for Neuroscience Newsletter ( more information )
Sign up to receive our recent neuroscience headlines and summaries sent to your email once a day, totally free.
We hate spam and only use your email to contact you about newsletters. You can cancel your subscription any time.