A novel intron mutation in FBN-1 gene identified in a pregnant woman with Marfan syndrome

Marfan syndrome (MFS) is one of the most common hereditary connective tissue diseases, with great individual heterogeneity. We reported a Chinese pregnancy with Clinical diagnosis of MFS, performed whole-exome sequencing, and screened for the genetic abnormality. We also conducted an in vitro mini-gene splicing assay to demonstrate the predicted harmful effects of an intronic variant of FBN-1. Exome sequencing identified a novel intronic variant (c.6497-13 T>A) in intron 53 of the FBN-1 gene (NM_000138.4). It’s predicted to insert 11 bp of intron 53 into the mature mRNA. The mini-gene splicing experiment demonstrated that c.6497-13 T>A could result in 11 bp retention in intron 53 to exon 54 (c.6496_6497ins gtttcttgcag) and the use of an alternative donor causing the frameshift p.Asp2166Glyfs*23. According to the results, the pregnant woman chose to continue the pregnancy and gave birth to a healthy baby. This study expands the genetic mutation spectrum of MFS patients and indicates the importance of intron sequencing. Supplementary Information The online version contains supplementary material available at 10.1186/s41065-020-00170-w.