Jean-Louis Mandel is a French geneticist, who was born and raised in Strasbourg. He completed his medical degree and Ph.D at the University of Strasbourg, and a postdoctoral fellowship at the Department of Medical Genetics at the University of Toronto.
In 1976, Mandel returned to France to continue his research on human genetic diseases in the laboratory of his mentor, Pierre Chambon. He went on to direct a molecular diagnostics laboratory at Strasbourg’s Regional and University Hospital Centre, and held the position of Professor of Human Genetics at the Collège de France from 2004 to 2016.
Mandel is currently Professor of Genetics at the Faculty of Medicine of the University of Strasbourg, and President of the French Foundation for Rare Diseases, based in Paris.
Mandel is a key contributor to the discovery of an unusual mutation mechanism in a gene on the X chromosome that causes Fragile X syndrome, an inherited form of intellectual disability, including autism and affecting males more severely. He showed that the mutation was a string of triple-letter repeats that disrupted the FMR1 gene. Such repeats results in the loss of the FMRP protein, which affect higher brain function. Mandel showed that the expression of the Fragile X syndrome depended on methylation inducing epigenetic modification at certain sites. Today, “unstable repeat expansions” are recognized as a common disease mechanism responsible for more than 50 genetic disorders. A familiar pattern has also emerged: when number of repeats increases in successive generations, symptoms arise earlier and are more severe. Understanding these unstable repeat expansions provides a model for numerous neurological diseases. Mandel´s work led to improvements in diagnosis.
He is a recipient of the 1999 Louis-Jeantet Prize for Medicine, the 2006 Grand Prix Foundation for Medical Research, and the 2009 Prize of the French National Academy of Medicine. He was made a Knight of the French Legion of Honour in 2008. He has been a permanent member of the French Academy of Sciences since 1999, and was elected as permanent member of the National Academy of Medicine in 2017.