Abstract
To assess the effect of Loeys-Dietz syndrome (LDS) mutations affecting TGFBR1 a selection of seven disease-associated amino acid substitutions were introduced into wild type TGF beta R1 and constitutively active TGF beta R1(T204D). Receptor function was tested by co-transfection with a luciferase reporter or EGFP-tagged SMAD2 in HEK293 cells. All of the mutations were found to be inactivating for canonical TGF-beta signaling. Differences in residual activity were not found to correlate with disease subtype. In co-transfection experiments with equal amounts wild-type receptor, the LDS mutations were found to confer a modest dominant negative effect. These results are discussed in relation to LDS and the related Marfan syndrome.