A Novel Heterozygous Intronic Mutation in the FBN1 Gene Contributes to FBN1 RNA Missplicing Events in the Marfan Syndrome

Figure 1

Schematic representation of in silico analysis of the c.2678-15C>A variant identified in intron 22 of the FBN1 gene by various computational tools. (a) Representation of the position of the canonical (c.2678, black triangle) and cryptic (c.2678-13, grey triangle) splice site identified in the reference (RS) and mutated sequence (MS), respectively. Arrow: the C to A point mutation (c.2678-15C>A). The intron 22 (i22) sequence is shown in lower case and exon 23 (E23) sequence in upper case. (b) The predicted splice score of the canonical site decreases by 29.8% and 49.7% in the mutated sequence (grey parallelogram) versus the reference sequence (black parallelogram) as revealed by the MES and GSP algorithm, respectively. (c) The predicted splice scores of a new cryptic splice site due to the c.2678-15C>A mutation.

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