We have been interested in understanding how mutations in these genes lead to human disease. LAM, which affects women almost exclusively, is a rare disease of pulmonary smooth muscle proliferation. Because of these similarities, we hypothesized that LAM and TSC have a common genetic basis. However, LAM is not genetically transmitted. Microscopically, there is cystic distortion of the normal pulmonary architecture by an infiltration of smooth muscle.
Most patients have a slowly declining clinical course.
Lung transplantation is the only effective therapy for patients with end-stage disease. We have demonstrated an interaction between hamartin and tuberin, which is detectable at endogenous protein levels. Hamartin is present in a cell line derived from the Eker rat that lacks functional tuberin, indicating that the stability of hamartin is not dependent on its interaction with tuberin. The P100 localization is unchanged in the Eker cells. Finally, we have shown that at endogenous expression levels hamartin has a punctate pattern of immunofluorescence in the cytoplasm.