Grant: Project Grant

This research project has the goal to identify new forms of hereditary diseases of the brain white matter. The white matter is made of myelin, an insulating material covering nerves and neurons and thus allowing the electrical conduction throughout the central nervous system. Damaged white matter, as it happens in white matter diseases, leads to disrupted nervous connections and causes neurological symptoms. Hereditary white matter diseases are suspected when multiple family members present similar symptoms, or when parents are related, or when a group of patients share the same symptoms and features. These disorders are considered rare among adults but emerging data from the scientific literature and our clinical practice suggest that they are often underdiagnosed or misdiagnosed. This lack or delay to achieve a genetic diagnosis has important repercussions on patients' life and their families. The identification of the causes of these diseases is a crucial step to elaborate a prognosis, offer genetic counselling and evaluate potential treatments. Magnetic Resonance Imaging (MRI) is the best technique to visualize the white matter. In this project we use an MRI protocol specifically designed to study the white matter. The goals of this research project are to characterize the MRI white matter abnormalities of patients with suspected genetic white matter diseases and identify the genes responsible for new forms of hereditary white matter diseases not yet diagnosed. In this study we will analyse MRI data to detect patterns of white matter involvement shared by multiple patients. We will then use next-generation genetic techniques, such as whole exome and genome sequencing, to identify the genes responsible for new forms of hereditary white matter diseases. With this study we expect to increase the number of diagnosed genetic white matter diseases, and ultimately reduce the diagnostic odyssey of affected patients.