Amélie Piton

Biography

Amélie Piton is associate professor and hospital practitioner (MCU-PH) in human molecular genetics of neurodevelopmental disorders. She is based at the Institute of Genetics and Molecular and Cellular Biology (IGBMC) of the University of Strasbourg. Her main research topics are the identification of mutations and genes involved in intellectual developmental disorders (IDD) and autism spectrum disorders (ASD), and the characterization of the pathophysiological mechanisms involved in some of these genetic forms.

After obtaining her PhD at Rennes University in France in 2005, Dr. Piton carried out postdoctoral training on the genetics of autism and schizophrenia at the University of Montreal (Canada) and, subsequently, on the genetics of intellectual disability at IGBMC. She obtained the habilitation to conduct research (HDR) in 2016. Since 2020, she is a leader of the IGBMC team “Genetics and pathophysiology of neurodevelopmental disorders (NDD)”. She is also, since 2014, a hospital practitioner within the molecular genetics unit of the Genetic Diagnosis Laboratory, University Hospital of Strasbourg (HUS).

From 2018 to 2023, Amélie Piton was a junior member of the Institut Universitaire de France (IUF). She is currently member of the scientific advisory boards of four patient associations and member of a specialised scientific commission (CSS) of the French National Institute of Health and Medical Research (Inserm). She is one of the coordinators of the Strasbourg Translational Research on the Autism Spectrum & Neurodevelopmental Disorders (STRAS&ND) and also of the French network for NDD diagnosis & IDD of the 2025 French genomic medicine initiative (PFMG2025).

Fellowship 2025

Dates - 01/12/2025-30/11/2027

Project summary

GENETIC MODIFIERS IN INTELLECTUAL DEVELOPMENT DISORDERS

Neurodevelopmental disorders (NDD), including intellectual developmental disorder (IDD), affect up to 2% of the population and often arise from rare genetic mutations. Despite major progress in identifying nearly 2,000 genes responsible for monogenic forms of NDD, significant clinical variability remains—even among individuals with the same genetic mutation. This poses challenges for diagnosis and genetic counselling. The project focuses on understanding why such variability exists and aims to identify modifier variants, i.e. additional genetic factors that may influence the severity of the disease.

This research centres on Argonaute (AGO) syndrome, caused by mutations in the AGO1 gene, a key player in RNA silencing pathways. Patients with identical mutations, such as Phe180del or Gly199Ser, show widely varying clinical symptoms, which makes AGO1 an ideal model to explore genetic modifiers. Amélie Piton’s team and her collaborators have already developed human neural stem cell and C. Elegans models carrying these mutations. They have also identified lists of genes dysregulated by AGO mutations in these models, which represent good candidate modifier genes. These models offer a unique opportunity to dissect how secondary genetic changes influence disease outcomes.

The project will proceed through four key steps: (1) collecting clinical and genomic data from known and new patients with AGO1 mutations; (2) generating a prioritized list of candidate modifier genes based on functional studies and bioinformatics; (3) identifying rare or impactful variants in these genes in patients with severe symptoms; and (4) validating the functional impact of these candidate modifiers using cellular and animal models.

The expected outcome is a pipeline to detect genetic modifiers in rare genetic forms of NDDs, starting with AGO syndrome. This would refine diagnosis and prognosis, guiding better personalized care. More broadly, the project offers a model for understanding clinical variability in other monogenic disorders and could lead to the identification of new therapeutic targets.