rs104893815

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.

This study screened 457 patients with suspected Marfan Syndrome (MFS), Loeys-Dietz Syndrome (LDS), and related connective tissue disorders for TGFBR2 and TGFBR1 mutations. The authors identified 23 TGFBR2 mutations (19 novel) and 6 TGFBR1 mutations with diverse clinical presentations ranging from classical MFS to isolated aortic aneurysm. Mutation detection rates were very low except in LDS patients (87.5%), suggesting these genes are responsible for a subset of disease cases with specific phenotypic features.