{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:14:41Z","timestamp":1761718481425},"reference-count":13,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,4,26]],"date-time":"2016-04-26T00:00:00Z","timestamp":1461628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec><jats:label \/><jats:p>Proteus syndrome (PS) is characterized by progressive, disproportionate, segmental overgrowth, and tumor susceptibility caused by a somatic mosaic <jats:italic>AKT1<\/jats:italic> activating mutation. Each individual has unique manifestations making this disorder extremely heterogeneous. We correlated three variables in 38 tissue samples from a patient who died with PS: the gross affection status, the microscopic affection status, and the mutation level. The <jats:italic>AKT1<\/jats:italic> mutation was measured using a PCR\u2010based RFLP assay. Thirteen samples were grossly normal; six had detectable mutation (2\u201329%) although four of these six were histopathologically normal. Of the seven grossly normal samples that had no mutation, only four were histologically normal. The mutation level in the grossly abnormal samples was 3\u201335% and all but the right and left kidneys, skull, and left knee bone, with mutation levels of 19%, 15%, 26%, and 17%, respectively, had abnormal histopathology. The highest mutation level was in a toe bone sample whereas the lowest levels were in the soft tissue surrounding that toe, and an omental fat nodule. We also show here that PS overgrowth can be caused by cellular proliferation or by extracellular matrix expansion. Additionally, papillary thyroid carcinoma was identified, a tumor not previously associated with PS. We conclude that gross pathology and histopathology correlate poorly with mutation levels in PS, that overgrowth can be mediated by cellular proliferation or extracellular matrix expansion, and that papillary thyroid carcinoma is part of the tumor susceptibility of PS. New methods need to be developed to facilitate genotype\u2013phenotype correlation in mosaic disorders. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37612","type":"journal-article","created":{"date-parts":[[2016,4,27]],"date-time":"2016-04-27T03:40:56Z","timestamp":1461728456000},"page":"1422-1432","source":"Crossref","is-referenced-by-count":20,"title":["Lack of mutation\u2013histopathology correlation in a patient with Proteus syndrome"],"prefix":"10.1002","volume":"170","author":[{"given":"Meggie E.","family":"Doucet","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Tulane University School of Medicine New Orleans Louisiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadley M.","family":"Bloomhardt","sequence":"additional","affiliation":[{"name":"Medical Genomics and Metabolic Genetics Branch National Human Genome Research Institute Bethesda Maryland"},{"name":"Yale School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krzysztof","family":"Moroz","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Tulane University School of Medicine New Orleans Louisiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjorie J.","family":"Lindhurst","sequence":"additional","affiliation":[{"name":"Medical Genomics and Metabolic Genetics Branch National Human Genome Research Institute Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie G.","family":"Biesecker","sequence":"additional","affiliation":[{"name":"Medical Genomics and Metabolic Genetics Branch National Human Genome Research Institute Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,4,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.17.2240"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201638"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3424"},{"key":"e_1_2_7_5_1","first-page":"75","volume-title":"Proteus syndrome. Overgrowth syndromes","author":"Cohen MM","year":"2002"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320570117"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(87)80249-9"},{"key":"e_1_2_7_8_1","first-page":"469","article-title":"Morphological characterization of the breast in Proteus syndrome complicated by ductal carcinoma in situ","volume":"36","author":"Iqbal J","year":"2006","journal-title":"Ann Clin Lab Sci"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1104017"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.312"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320350228"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:APPT.0000045801.15585.dd"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2004.12.047"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35764"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37612","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37612","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T09:49:32Z","timestamp":1696585772000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37612"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,26]]},"references-count":13,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["10.1002\/ajmg.a.37612"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37612","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,26]]}}}