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Description
Autism has been at the forefront of basic and clinical research worldwide. It have been proven that the identification of new etiologic/risk factors, as well as early diagnosis - thus allowing early therapeutic approaches -, have great beneficial effects on patients’ condition and on the overall costs supported by the society. Although a great amount of information has been accumulating at a very high speed, the clinical heterogeneity, complex genetic architecture and multisystemic characteristic of autism pose particular challenges for healthcare professionals. Thus, autism still require refined clinical, imagistic, genetic, and computing tools for characterization as well as translation into knowledge databases and ultimately to clinical practice. The present project is an example of a translational approach, from clinical characteristics, neurobiological and genetic mechanisms to clinical populations, and thus very relevant for human diseases and health. By consolidating a knowledge database, both Romanian and Norwegian teams aim to increase the application of research results in the field of autism. The complex evaluation of a big cohort of patients with autism will contribute not only to the establishment of the Romanian Registry for autism, but will also offer important data for estimation of autism prevalence in Romania, for improving the early diagnosis and for a better understanding of its mechanisms. This project brings together a consortium consisting of one Norwegian and two Romanian institutions with strong expertise in their field of activity. The three partners form an integrated multi-disciplinary team with complementary expertise leading to synergy.With the present project, OHP (CO) and the Norwegian partner (OU: University of Oslo and Oslo University Hospital) consolidate a network of already established collaboration in the frame of an ERA-NET Neuron project focused on schizophrenia research.
Summary of project results
Autism spectrum disorders (ASDs) are complex neurodevelopmental conditions often accompanied by other neuropsychiatric disorders. Identification of new etiologic/risk factors, as well as early diagnosis which allows early therapeutic approaches, have great beneficial effects on patients’ quality of life and on the overall costs supported by the society. The clinical heterogeneity, complex genetic architecture and multisystemic nature of ASDs continue to be challenging for healthcare professionals. Thus, ASDs require refined clinical, imagistic, genetic, and computing tools for characterization as well as translation to clinical practice. Currently, genetic testing of ASD patients in Romania is still limited, with few centers available and often limited financial resources allocated. The lack of a National Registry for ASD in Romania is another problem which impacts significantly systematic health care planning and decision making at national level. The complex evaluation of a big cohort of patients with ASDs contributes to generation of clinical and genetic databases, valuable data sources for the establishment of the Romanian Registry for ASD. In addition, data generated by the clinical, bioimaging and genomic approaches will serve as a starting point for developing predictive tools, especially for comorbidities in ASDs, as well as medical and social strategies planning
The main activities of the project included enrollment of patient and control groups, deep clinical phenotyping of patients with ASDs, neuroimaging evaluation, and genetic investigations using genome-wide (array-CGH, sequencing) and targeted approaches (fragile X syndrome etiologic testing). The output was represented by genetic data, such as genomic profiles obtained by chromosomal microarray, FMR1 methylation profiles / repeat expansion evaluation (male patients) and sequencing data. Data analysis activities integrated all data and allowed phenotype-genotype correlations, clinical interpretation of genetic and MRI findings as well as statistical analyses. These activities led to the establishment of clinical, neuroimagistic and genetic data sets, and the set-up of a database. Besides the contribution to a better understanding of the genetic mechanisms of ASD, the data represented the foundation for elaboration and development of the Romanian Registry of patients with ASD. Although the Registry data recording have started with the patients with ASDs enrolled in this study, other patients with ASD evaluated in our hospital will also be included. Part of our project results were published in international journals with a high visibility, and were presented at national and international scientific manifestations. A project website was created for dissemination of project activities and results.
Our project generated significant results for the patients with ASDs and the specialists involved in their management. Thus, a complex protocol evaluation for early diagnosis of ASD, which includes clinical, dysmorphological, and psychologic evaluation, MRI studies, and genetic tests, was developed. Our project demonstrated the important role of genetic studies for the identification of ASD etiology and the establishment of optimal protocols for interrogation of known syndromic ASDs genetic changes and characterization of rare genomic and sequence variants with clinical relevance. This complex evaluation of patients with ASD generated a personalized management plan, including both recommendation for specific therapies and follow-up plan. These results also helped the doctors from different specialties to improve their knowledge in the field of ASD. An important result of our project was the registry for patients with ASD which will offer data for further epidemiological, clinical and genetic studies. This information can be used by the health care authorities to further develop public the health policies for ASD. Thus, the results of our project will help the translation of multidisciplinary data into predictors for disease trajectory of ASD and personalized decision making, such as stratify interventions and treatment.
Summary of bilateral results
The joint activities of our consortium enhanced the expertise and research capability of the Romanian institutions in areas such as clinical and imagistic research, and genomics (next generation sequencing, big data analysis and data management). This collaborative effort increased the scientific level of Romanian research and improved the diagnosis and management of this condition. With the present project, OHP (PP) and the Norwegian partner OU (P1) consolidate and enlarge an already existing collaboration set-up in the frame of an ERA-NET Neuron project focused on schizophrenia research. All the above-mentioned represent the foundation of a long-term partnership between Romania and Norway in the field of the most common psychiatric conditions.