{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T20:30:04Z","timestamp":1774125004132,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,7,15]],"date-time":"2004-07-15T00:00:00Z","timestamp":1089849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Internal Medicine"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:title>Abstract.<\/jats:title><jats:p><jats:bold>Background:\u2002<\/jats:bold>Lymphangioleiomyomatosis (LAM) can occur as in isolated form (sporadic LAM) or as a pulmonary manifestation of tuberous sclerosis complex (TSC) (TSC\u2010associated LAM). Recent studies, however, revealed that both forms of LAM are genetically related but that sporadic LAM is a distinct clinical entity caused by somatic mutations of<jats:italic>TSC2<\/jats:italic>(not<jats:italic>TSC1<\/jats:italic>) rather than a forme fruste of TSC carrying either of the<jats:italic>TSC1<\/jats:italic>or<jats:italic>TSC2<\/jats:italic>germline mutations.<\/jats:p><jats:p><jats:bold>Method:\u2002<\/jats:bold>Case presentation and in\u2010depth molecular and histopathological examinations. A 34\u2010year\u2010old Japanese woman was diagnosed as having pulmonary lymphangioleiomyomatosis (LAM) when bilateral pneumothoraces were surgically treated in 1992. Although slowly progressive renal disfunction was observed due to bilateral multiple renal cysts during the past 4 years, she had no other clinical features of TSC and was diagnosed as having sporadic LAM with multiple renal cysts of undetermined aetiology. Her subsequent clinical course was complicated by an endobrochial carcinoid tumour, which eventually resulted in her death in June 1999 due to massive haemoptysis.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold>Postmortem examination revealed the presence of LAM lesions in the lungs, mediastinal lymph nodes, kidneys and uterus. Diffuse renal LAM lesions are presumed to generate multiple renal cysts by constricting the nephron rather than epithelial hyperplasia obstructing lumina, which is analysis of the<jats:italic>TSC<\/jats:italic>genes demonstrated that she did not have<jats:italic>TSC2\/PKD1<\/jats:italic>contiguous gene syndrome but had a<jats:italic>TSC<\/jats:italic>1 germline mutation (Sato T<jats:italic>et al<\/jats:italic>. J Hum Genet 2002;<jats:bold>47<\/jats:bold>: 20\u20138) that had occured<jats:italic>de novo<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold>This patient therefore illustrates that clinical manifestations of TSC are sufficiently diverse as to allow a forme fruste of TSC that mimics sporadic LAM and that<jats:italic>TSC<\/jats:italic>1 mutation can cause multiple renal cysts resulting in renal failure.<\/jats:p>","DOI":"10.1111\/j.1365-2796.2004.01356.x","type":"journal-article","created":{"date-parts":[[2004,7,15]],"date-time":"2004-07-15T13:25:45Z","timestamp":1089897945000},"page":"166-173","source":"Crossref","is-referenced-by-count":18,"title":["A patient with<i>TSC1<\/i>germline mutation whose clinical phenotype was limited to lymphangioleiomyomatosis"],"prefix":"10.1111","volume":"256","author":[{"given":"T.","family":"Sato","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Seyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Kumasaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Setoguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Shirai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Tomino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O.","family":"Hino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Fukuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,7,15]]},"reference":[{"key":"e_1_2_8_2_2","first-page":"977","article-title":"Lymphangioleiomyomatosis. 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