Mutations in fibrillin-1 gene (FBN1) have been shown to be associated with Marfan syndrome and most FBN1 mutations display missense or nonsense. Recently, reports on synonymous mutation-related diseases have attracted widespread attention. Zhang et al demonstrated that synonymous mutations in saccharomyces cerevisiae have pathogenicity like non-synonymous mutations.1 Based on a special Marfan syndrome patient with a novel synonymous mutation in FNB1, this study aimed to investigate the pathogenic mechanism of synonym mutation, hoping to explore individualized precision therapy to improve or even cure those diseases caused by synonymous mutations. Through the current study, we naturally come to the following conclusions: mutations within the exon that was away from canonical splicing sites might lead to aberrant splicing, by generating splicing regulatory elements (SRE) and leading to alterations in SRE-binding proteins and thus breaking the splicing balance. Studies on the regulatory process of gene splicing in genetic diseases are expected to provide new prospects for individualized targeted therapy.