Marfan syndrome, a human disease involving cardiovascular and skeletal apparatuses and ocular and central nervous systems, is associated to mutations in FBN1 gene; heterozygous mutations in TGFBR2 and TGFBR1 genes were found associated to MFS type 2, characterized by the presence of skeletal and cardiovascular major criteria and absence of eye major criterion. We screened the TGFBR1 gene in 46 Marfan patients in whom mutations in FBN1 and TGFBR2 genes were excluded and the analysis of Ex1 was extended to additional 114 Marfan patients and 237 controls. We detected two potentially pathological sequence variants: the TGFBR1 6Ala allele whose frequency was higher in the group of Marfan patients (0.13) than in the controls (0.08) (p = 0.013; OR = 1.69) and an insertion of 20 nucleotides in the 5′UTR that turned out to be a familial silent rare polymorphism. We hypothesize that TGFBR1 sequence variants may act not only as major, but also as low penetrance alleles of the clinical phenotype in Marfan syndrome.
- Marfan syndrome
- MFS type 2
- TGFBR1 6Ala allele
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine