{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:06:59Z","timestamp":1789445219206,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,8,6]],"date-time":"2007-08-06T00:00:00Z","timestamp":1186358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2007,9]]},"abstract":"<jats:p>The diagnosis of Marfan syndrome may be hampered by the existence of very mild and atypical cases as well as by marked intrafamilial variability. In these instances, molecular analysis of the fibrillin\u20101 gene (<jats:italic>FBN1) <\/jats:italic>can be helpful to identify individuals at risk. The underlying molecular mechanism for the clinical variability is presently unknown. We performed clinical and molecular studies in 36 subjects from three unrelated families. Expression studies of both <jats:italic>FBN1 <\/jats:italic>alleles were performed and related to the clinical severity. In family 1, an overlapping phenotype between Marfan syndrome (MFS) and Weill\u2013Marchesani syndrome is presented. The diagnosis necessitated molecular studies and clinical examination in first\u2010degree relatives. In family 2, the young proband presented with a phenotype overlapping between MFS and the kyphoscoliotic type of Ehlers\u2013Danlos syndrome. Follow\u2010up over time and identification of a <jats:italic>FBN1 <\/jats:italic>mutation allowed confirmation of the diagnosis. Mutation analysis enabled us to identify family members with mild expression. Family 3 illustrates the extensive intrafamilial variability in the clinical severity of MFS. Identification of a <jats:italic>FBN1 <\/jats:italic>mutation was helpful to identify subjects with mild expression and for the timely diagnosis in a neonate. In families 2 and 3, the relative expression of both <jats:italic>FBN1 <\/jats:italic>alleles was not related to clinical severity. We demonstrated that confirmation of the diagnosis of MFS may require detailed and repeated clinical evaluation and thorough family history taking. <jats:italic>FBN1 <\/jats:italic>mutation analysis is supportive for the diagnosis in mild and atypical presentations.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2007.00845.x","type":"journal-article","created":{"date-parts":[[2007,8,7]],"date-time":"2007-08-07T06:10:16Z","timestamp":1186467016000},"page":"188-198","source":"Crossref","is-referenced-by-count":45,"title":["Utility of molecular analyses in the exploration of extreme intrafamilial variability in the Marfan syndrome"],"prefix":"10.1111","volume":"72","author":[{"given":"J","family":"De Backer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Loeys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Leroy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Coucke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Dietz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"De Paepe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,8,16]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/352337a0"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19960424)62:4<417::AID-AJMG15>3.0.CO;2-R"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199407213310302"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(00)80066-1"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg241"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(89)90430-X"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)12448-0"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/pd.223"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/1.7.542"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115766"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-51-5-1049"},{"key":"e_1_2_6_13_2","first-page":"337","article-title":"Marfan\u2019s syndrome: the S. family re\u2010visited","volume":"89","author":"Bowers D","year":"1963","journal-title":"Can Med Assoc J"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/425231"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.1.34"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10249"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19960329)62:3<233::AID-AJMG7>3.0.CO;2-U"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002469900493"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.161.20.2447"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10112"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.10.1581"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471221929.ch9"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(94)90762-5"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380110164"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1392"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1399-0004.2007.00845.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1399-0004.2007.00845.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T15:46:10Z","timestamp":1696866370000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1399-0004.2007.00845.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,8,16]]},"references-count":24,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2007,9]]}},"alternative-id":["10.1111\/j.1399-0004.2007.00845.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1399-0004.2007.00845.x","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,8,16]]}}}