{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T17:49:42Z","timestamp":1760982582843,"version":"build-2065373602"},"reference-count":46,"publisher":"BMJ","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:sec>\n                  <jats:title>Background:<\/jats:title>\n                  <jats:p>Cowden disease is an autosomal dominant syndrome predisposing to cancer and characterised by the occurrence throughout life of hyperplastic, hamartomatous and tumoural lesions affecting various organs. In 60\u201380% of patients a germline intragenic point mutation of the <jats:italic>PTEN<\/jats:italic> tumour suppressor gene is identified, but at least 20% of patients with a well characterised phenotype remain without any identified mutation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>To evaluate the impact of large rearrangement involving the <jats:italic>PTEN<\/jats:italic> locus in Cowden disease, we analysed by a multiplex amplifiable probe hybridisation (MAPH) technique 80 unrelated patients referred for diagnosed or suspected Cowden disease, and in whom no <jats:italic>PTEN<\/jats:italic> point mutation was detected by a denaturing gradient gel electrophoresis (DGGE) screening.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>Four heterozygous genomic deletions involving the <jats:italic>PTEN<\/jats:italic> gene were identified. These deletions ranged from 13.6\u2013662 kb and are restricted to the <jats:italic>PTEN<\/jats:italic> locus in two cases. In the two other cases, the deletion encompassed <jats:italic>PTEN<\/jats:italic> and either two or three contiguous genes without any obvious phenotypic effect, except a possible consequence of <jats:italic>PAPSS2<\/jats:italic> haploinsufficiency on bone growth. Sequence analysis of the four deleted alleles did not reveal identity or sequence homology at the two breakpoints of a same allele, suggesting that a mechanism such as non-homologous recombination of the breakage and reunion type could lead to the occurrence of these deletions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion:<\/jats:title>\n                  <jats:p>Large rearrangements of the <jats:italic>PTEN<\/jats:italic> gene can be involved as causing mutation in Cowden disease and MAPH is an efficient screening methodology to detect such a genetic alteration.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2008.058131","type":"journal-article","created":{"date-parts":[[2008,5,4]],"date-time":"2008-05-04T07:54:05Z","timestamp":1209887645000},"page":"657-665","source":"Crossref","is-referenced-by-count":14,"title":["Contribution of <i>PTEN<\/i> large rearrangements in Cowden disease: a multiplex amplifiable probe hybridisation (MAPH) screening approach"],"prefix":"10.1136","volume":"45","author":[{"given":"F","family":"Chibon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Primois","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J-M","family":"Bressieux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Lacombe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Lok","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Mauriac","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Taieb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Longy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2008,5,2]]},"reference":[{"key":"2025100521461596000_45.10.657.1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025664119494"},{"key":"2025100521461596000_45.10.657.2","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2007.07.009"},{"key":"2025100521461596000_45.10.657.3","doi-asserted-by":"publisher","DOI":"10.1038\/ng0897-333"},{"key":"2025100521461596000_45.10.657.4","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.35.11.886"},{"key":"2025100521461596000_45.10.657.5","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201823"},{"key":"2025100521461596000_45.10.657.6","doi-asserted-by":"publisher","DOI":"10.1038\/ng0597-64"},{"key":"2025100521461596000_45.10.657.7","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.3.507"},{"key":"2025100521461596000_45.10.657.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(03)00175-2"},{"key":"2025100521461596000_45.10.657.9","doi-asserted-by":"publisher","DOI":"10.1002\/1098-1004(200008)16:2<109::AID-HUMU3>3.0.CO;2-0"},{"key":"2025100521461596000_45.10.657.10","doi-asserted-by":"publisher","DOI":"10.1086\/504301"},{"key":"2025100521461596000_45.10.657.11","doi-asserted-by":"publisher","DOI":"10.1086\/377109"},{"key":"2025100521461596000_45.10.657.12","doi-asserted-by":"publisher","DOI":"10.1038\/ng0596-114"},{"key":"2025100521461596000_45.10.657.13","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.2.605"},{"key":"2025100521461596000_45.10.657.14","first-page":"35","article-title":"Cowden disease. 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