rs334354

This study developed and validated a multiplex PCR-based next-generation sequencing (NGS) workflow for identifying mutations in FBN1, TGFBR1, and TGFBR2 genes associated with Marfan and Loeys-Dietz syndromes. In 87 Marfan syndrome patients, the NGS workflow identified 72 unique FBN1 mutations (57 novel), with an overall mutation identification rate of 92% (80/87 patients). Of the 72 FBN1 mutations, 34 were missense (24 involving cysteines), 15 frameshift, 9 nonsense, 9 splice-site, 4 large rearrangements, and 1 in-frame deletion, with complementary MLPA analysis detecting 4 large deletions/insertions.

A literature review summarizing epidemiologic evidence for associations between genetic polymorphisms in TGF-β signaling pathway genes and breast cancer risk and survival. The TGFB1 T+29C polymorphism (rs1982073) is the most studied variant, with meta-analysis showing a summary OR of 0.92 (95% CI=0.81-1.05) for CC genotype versus TT; results across studies were inconsistent. The TGFBR1 9A/6A polymorphism showed evidence of elevated risk with the *6A allele in some studies. For survival, TGFB1 variant C allele carriers showed reduced disease-free survival (HR=1.4, 95% CI=1.0-1.9) in one major study.