Generalized mosaicism for TSC2 mutation in isolated Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a rare, slowly progressive pulmonary disease, causing cystic lung destruction and respiratory failure. It affects predominantly premenopausal women, and rarely men. It can occur as a sporadic condition (sporadic LAM) or in association with Tuberous Sclerosis Complex (TSC-LAM) [1]. LAM is caused by biallelic inactivation of the tumor suppressor gene TSC2 in LAM cells, which leads to hyperactivation of mTORC1, resulting in anabolism and LAM cell proliferation [2]. Sirolimus and everolimus, mTORC1 allosteric inhibitors, have been shown to retard progression of LAM [3]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Ogorek has nothing to disclose. Conflict of interest: Dr. Hamieh has nothing to disclose. Conflict of interest: Ms. Lasseter has nothing to disclose. Conflict of interest: Dr. Bagwe has nothing to disclose. Conflict of interest: Dr. Thorner has nothing to disclose. Conflict of interest: Dr. Nag has nothing to disclose. Conflict of interest: Dr. Gulleman has nothing to disclose. Conflict of interest: Dr. Giannikou has nothing to disclose. Conflict of interest: Dr. Young reports grants from The LAM Foundation, during the conduct of the study; other from Boehringer Ingelheim, other from UpToDate, outside the submitted work; In addition, Dr. Young has a patent VEGF-D in diagnosis of LAM licensed to Cincinnati Children's (no personal royalties). Conflict of interest: Dr. Pujana reports grants from Roche Pharma, outside the submitted work. Conflict of interest: Dr. Darling has nothing to disclose. Conflict of interest: Dr. El-Chemaly has nothing to disclose. Conflict of interest: Dr. Moss has nothing to disclose. Conflict of interest: Dr. Henske has nothing to disclose. Conflict of interest: Dr. Kwiatkowski has nothing to disclose. Conflict of interest: Dr. Herranz has nothing to disclose. Conflict of interest: Tania Machado has nothing to disclose.