ENCode-ID: Elucidating the contribution of coding and Non-Coding genomic variations to Intellectual Disability for therapeutic discovery

Intellectual disability, also referred to as intellectual development disorder (IDD), is a neurodevelopmental condition that causes a wide range of disability, profoundly affecting the lives of patients and their families. IDD affects 1 to 3% of the world's population, i.e. several million people, hence representing a major public health challenge. It is predominantly of genetic origin and displays the greatest gene heterogeneity of all genetic disorders. Among the main challenges related to IDD are, on the one hand, the lack of molecular diagnosis in more than 50% of cases, despite the use of state-of-the-art genetic technologies, and on the other hand, the lack of therapeutic avenues. EnCode-ID aims to address these by elucidating the impact of different types of genomic variations including those in the non-coding genome.

The ENCode-ID project, led by Dr. Laïla El Khattabi, aims to identify new genetic causes of intellectual disability (IDD), unravel markers of severity, and pave the way toward therapeutic strategies.

Based on genetic data from nearly 500 children and using an innovative functional genomics strategy combining high-throughput genome editing, brain organoids, and advanced phenotyping methods, the research team will investigate the impact of thousands of genetic variations (located in genes with poor or not known function or in gene regulatory regions) on early brain development. The resulting data will then be analyzed using artificial intelligence tools to identify prognosis markers and potential therapeutic targets.

Improving the molecular diagnosis of IDD will help adapt care pathways, facilitate connections between families facing the same genetic causes, thus fostering peer support. Reducing diagnostic delays will also allow financial resources to be redirected toward more direct and effective care while improving families’ psychological well-being. Finally, the search for therapeutic avenues represents an innovative line of research and a source of hope for a condition still considered incurable.