​With more than 7,000 diseases identified to date, affecting a total of 3 million people in France, the diagnosis of rare diseases is a major public health challenge. Rendu-Osler disease is a rare genetic disorder whose symptoms worsen with age. Patients suffer in particular from frequent and profuse nosebleeds, which can sometimes require blood transfusions. The disease can also cause malformations between veins and arteries in vital organs (such as the liver, lungs, and brain), which can rupture and cause hemorrhages. Not all of the genetic mutations responsible for the disease have yet been properly identified, delaying diagnosis—and, consequently, patient care—by several months. The goal of our study is to help doctors and hospital laboratories make a diagnosis more quickly.

Researchers at CEA-Irig/Biosanté work closely with the Hospices Civils de Lyon, the national reference center for Rendu-Osler disease. Using blood samples from patients with an uncertain diagnosis, mutations in a gene (GDF2) were detected, although their link to the disease had not been clearly established. In the laboratory, we reproduced these mutations and developed an in vitro cellular assay in which we tested the biological activity of the proteins carrying these mutations. If the activity is normal, the mutation is considered benign. However, if the activity is reduced, this means that the mutation prevents the protein from functioning normally. The mutation is then considered pathological and contributes to the development of the disease.