%0 Journal Article
%T TGFBR3 variation is not a common cause of Marfan-like syndrome and Loeys-Dietz-like syndrome
%A Krishna K Singh
%A Joerg Schmidtke
%A Britta Keyser
%A Mine Arslan-Kirchner
%J Journal of Negative Results in BioMedicine
%D 2012
%I BioMed Central
%R 10.1186/1477-5751-11-9
%X Marfan syndrome (MFS; MIM# 154700) is an autosomal-dominant disorder of connective tissue with major manifestations in the skeletal, cardiovascular and ocular systems. MFS is caused by mutations in the fibrillin-1 gene (FBN1), and mutations in FBN1 are known to be responsible for over 90% of all MFS cases. However, locus heterogeneity was reported in the early 1990's, when a second locus 3p24.2-p25 was suggested to cause MFS [1]. This association was further confirmed when mutations were identified in the transforming growth factor £¿ receptor type II gene (TGFBR2), which maps to the corresponding chromosomal region, in patients with overlapping phenotypes of MFS and Loeys-Dietz syndrome (LDS1B; MIM#610168) [2-4]. Later, using a functional approach, mutations were identified in another receptor of TGF-£¿ receptor family, transforming growth factor £¿ receptor type I (TGFBR1) in association with MFS or related phenotypes LDS (LDS1A; MIM#609192) [3-5]. These and other findings, strongly suggested an important role played by TGF-£¿ receptors and TGF-£¿ signaling dysregulation in the pathogenesis of MFS and related phenotypes [6,7]. The TGF-£¿ signaling pathway regulates extracellular matrix formation through members of the TGF-£¿ superfamily and their receptors [8]. TGF-£¿ mainly functions by binding to three cell surface receptors, namely TGFBR1 (55 kD), TGFBR2 (80 kD) and transforming growth factor receptor type III (TGFBR3, 280 kD) [9]. TGFBR3 is the most abundantly expressed subtype, has high affinity for all three TGF-£¿ isoforms, and acts as an enhancer of the TGF-£¿ access to the other signaling receptors [10]. So far, no systematic search for TGFBR3 genetic variation associated with MFS and related phenotypes has been reported in the literature. To test the hypothesis that dysregulation of TGFBR3-associated TGF-£¿ signaling is implicated in MFS or related phenotype pathogenesis, we selected a cohort of 49 patients, fulfilling or nearly fulfilling the diagnostic criteria f
%K MFS
%K LDS
%K TGFBR3
%K variants
%U http://www.jnrbm.com/content/11/1/9