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Analysis of TGFBR1*6A variant in individuals evaluated for Marfan syndrome
Author(s) -
Somers Allyson E.,
Hinton Robert B.,
Pilipenko Valentina,
Miller Erin,
Ware Stephanie M.
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37668
Subject(s) - marfan syndrome , allele , ectopia lentis , penetrance , connective tissue , phenotype , genetics , connective tissue disorder , medicine , allele frequency , bioinformatics , biology , pathology , gene
Marfan syndrome (MFS) and Loeys–Dietz syndrome (LDS) are genetic disorders that affect connective tissue as a result of dysregulated TGF‐β signaling. MFS is most frequently caused by mutations in FBN1 whereas Loeys–Dietz syndrome results from mutations in TGFBR1 or TGFBR2 . There is substantial inter‐ and intra‐familial phenotypic variability among these disorders, suggesting the presence of genetic modifiers. Previously, a polymorphism in the TGFβR1 protein termed the TGFBR1*6A allele was found to be overrepresented in patients with MFS and was identified as a low penetrance allele with suggestion as a possible modifier. To further investigate the importance of this variant, a retrospective review of genetic and phenotypic findings was conducted for 335 patients evaluated for suspicion of MFS or related disorders. In patients with a diagnosis of MFS, the presence of the TGFBR1*6A allele was not associated with phenotypic differences. Similarly, careful phenotyping of patients who carried the TGFBR1*6A allele but did not have MFS did not identify an altered frequency of specific connective tissue features. In this small cohort, the results did not reach significance to identify the TGFBR1*6A allele as a major modifier for aortic dilation, ectopia lentis, or systemic features associated with MFS or other connective tissue disorders. © 2016 Wiley Periodicals, Inc.