A study identifies new genetic alterations involved in the development of Autism Spectrum Disorders

It is a pioneering study as it is the first to use the integration of genome sequencing together with blood RNA as a strategy to identify the genetic causes of Autism Spectrum Disorders (ASD). The goal of the research, as Ivon Cuscó points out "is to better understand the biological defects implicated in these disorders in order to provide diagnostic tools to the families affected". Specifically, patients from throughout Spain were studied in whom so far no genetic alteration had been detected.

The research, published in the journal Molecular Autism, has been led by Ivon Cuscó and Luis Pérez Jurado, researchers at the Genetics Unit of the Department of Experimental and Health Sciences (CEXS) of UPF, and members of the CIBERER network for the study of rare diseases, and is the result of the doctoral research project by Marta Codina, first author of the article.

The main results obtained have helped to identify new genetic alterations or mutations that, independently, are involved in the development of ASD. Fourteen percent of them were de novo mutations, that is to say, appearing in the patient without the parents having them; and 5% were hereditary and linked to the X chromosome.

Both basic and clinical (attending to patients and their families) researchers have participated in this study. The collaboration between the two has been essential not only to carry out the study, but because the direct implication of this type of research in daily clinics is increasingly important. In this sense, "this study is relevant to advance in the understanding of the biological bases of ASD, and also because it has a direct and practical application because it means genetic counselling can be provided for the affected families. That is to say, explaining to the mothers and fathers of the affected children, or their relatives, the likelihood of a similar disorder recurring if they have another child, for example", says Ivon Cuscó.

In addition, the research confirms that among patients diagnosed with ASD, some have only one genetic mutation, which is responsible for it (monogenic form), while others have an accumulation of are rare or uncommon mutations. In the latter case, the team of researchers has determined that these rare mutations alter certain pathways involved in the cellular functioning and development of the nervous system, and this could be related to the onset of symptoms.

Besides, using this data integration strategy they have managed to determine the defect caused by some of the mutations, detecting that altered genes are badly expressed in the patients' blood.

What are Autism Spectrum Disorders?

ASD include a group of neurobehavioural syndromes characterized by deficiencies in social interaction, impaired communicative ability and restrictive and repetitive patterns of behaviour; symptoms that appear before the age of 3. Almost one in every 100 children suffers ASD, and the frequency is four times higher in boys than in girls. It is one of the most heritable neuropsychiatric disorders and is considered a multifactorial disease that involves several genes. Currently, the cause of the onset of this disorder can be explained in only 30% of cases, remaining unknown to the majority of patients. The breakthroughs in new technologies are paving the way for increasing this percentage and therefore the knowledge of the causes involved.

Reference work

Marta Codina-Solà, Benjamín Rodríguez-Santiago, Aïda Homs, Javier Santoyo, Maria Rigau, Gemma Aznar-Laín, Miguel del Campo, Blanca Gener, Elisabeth Gabau, María Pilar Botella, Armand Gutiérrez-Arumí, Guillermo Antiñolo, Luis Alberto Pérez-Jurado, Ivon Cuscó (2015) " Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders". Molecular Autism DOI: 10.1186/s13229-015-0017-0