Discovery of the genetic basis of two diseases

In a first article, Loeys et al describe a new aortic aneurysm syndrome characterized by the main triad of hypertelorism, bifid uvula and/or cleft palate and aortic aneurysms with arterial tortuosity. This new entity also presents with alterations of the skeletal, craniofacial, neurocognitve development. Importantly, the nature of the aortic aneurysms seems very aggressive and aneurysms occur throughout the arterial tree. In a collaboration between Johns Hopkins University in Baltimore and Ghent University in Belgium, it was demonstrated that this disease is caused by mutations in either of the genes encoding for transforming growth factor receptor 1 or 2 (TGFBR1 or 2).

In a second article, homozygosity mapping of a Senior-Loken family evaluated at the Ghent University led to the idenfication of a region on the long arm of chromosome 3. Researchers of the Ann Harbor University in Michigan went on to clone a new gene, nephrocystin-5, a ciliary IQ domain protein. Senior-Loken syndrome is characterized by the association of nephronophtisis and retinitis pigmentosa. These studies emphasize the central role of ciliary dysfunction in the pathogenesis of Senior-Loken syndrome.