10% of early diabetes are atypical (not classified DT1 or DT2). However, 80% of these diabetes have a monogenic origin for which effective personalized treatments are possible. These monogenic forms are also present in 5% of T2DMs and 5% of childhood obesity. The development of Next Generation Sequencing (NGS) methods reveals the possibility of a targeted molecular diagnosis allowing personalized genomic medicine.
Person in charge: Dr. Amélie Bonnefond
Genomic medicine for diabetes
T2D is indeed considered a complex genetic disease : most T2D is considered to be “polygenic forms” which depend on multiple common genetic variants acting in combination with environmental risk factors. However, there are also rarer and generally more severe forms known as “monogenic forms”, in which a single constitutional genetic mutation is sufficient to cause diabetes most often at an early age. Genetic investigations of these monogenic forms have revealed crucial players involved in the development and function of pancreatic β cells, leading to the discovery of real “case studies” of personalized genomic medicine.
In this project, we wish to sequence the genes involved in monogenic forms of diabetes and associated diseases in patients with T2D in order to launch an interventional study on the adaptation of treatment and / or the specific clinical investigation of organs. The aim is to assess the effectiveness of these interventions for patients and the gains in terms of public health.
Responsable : Prof. Philippe Froguel
Genomic medicine for obesity
In some countries, up to 25% of children are obese, suggesting a reduction in their life expectancy of 5 to 10 years. Childhood obesity is the dominant risk factor for persistent adult obesity and is associated with delayed schooling and harmful social isolation. Often overlooked, obesity puts many patients at a diagnostic and therapeutic level.
Common obesity is a multifactorial disease. However, there is a monogenic component of obesity (phenotypically isolated or syndromic) with disruption of the hypothalamic appetite control circuits. We estimate that in France at least 10,000 children have a monogenic form of obesity, most of them neither being diagnosed nor cared for properly. We were pioneers and world leaders in identifying the various obesity genes. Recently, a medicament (setmelanotide – MC4R agonist) has been shown to reduce hunger for a long time and allow significant weight reduction in carriers of pathogenic mutations in the melanocortin pathway.
Here we will analyze the genome of children and adults with suspected monogenic obesity undiagnosed to date, and through this project we intend to unlock the diagnostic locks of severe monogenic obesity paving the way for efficient precision medicine.