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TGFBR1 and TGFBR2 mutations in patients with features of Marfan syndrome and Loeys‐Dietz syndrome
Author(s) -
Singh Krishna Kumar,
Rommel Kathrin,
Mishra Anjali,
Karck Matthias,
Haverich Axel,
Schmidtke Jörg,
ArslanKirchner Mine
Publication year - 2006
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20354
Subject(s) - marfan syndrome , connective tissue disorder , biology , mutation , fibrillin , genetics , point mutation , gene , pathology , medicine
Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder characterized by manifestations in the cardiovascular, skeletal, ocular, and other organ systems. MFS type1 (MFS1) is caused by mutations in the gene encoding fibrillin ( FBN1 ). Recently, the transforming growth factor‐β receptor‐2 gene, TGFBR2 , has been shown to be associated with a second type of this disorder with typically mild or absent ocular involvement (MFS type 2; MFS2). Several point mutations were found in the highly conserved serine/threonine kinase domain of TGFBR2 . Mutations in both TGFBR1 and TGFBR2 are associated with Loeys‐Dietz aortic aneurysm syndrome (LDS). We searched for TGFBR1 and TGFBR2 mutations in 41 unrelated patients fulfilling the diagnostic criteria of Ghent nosology or with the tentative diagnosis of Marfan syndrome, in whom mutations in the FBN1 coding region were not identified. In TGFBR1 , two mutations and two polymorphisms were detected. In TGFBR2 , five mutations and six polymorphisms were identified. Reexamination of patients with a TGFBR1 or TGFBR2 mutation revealed extensive clinical overlap between patients with MFS1, MFS2, and LDS. Hum Mutat 0, 770–777, 2006. © 2006 Wiley‐Liss, Inc.