Fig. 2

WES identified a novel FBN1 mutation [NM_000138.5; c.7764 C > G: p.(Y2588*)] and thestructural reconstruction. (A). BAM illustration of WES in the proband’s family of four. The gray area indicated the second-generation capture coverage. At position c.7764, the C/G ratio is as follows: C: 103 (forward: 35 +, reverse: 68 -), comprising 47% of the total; G: 116 (forward: 42 +, reverse: 74 -), comprising 53% of the total. (B). The Sanger sequence of other 4 family members showed no mutation in c.7764. (C). Protein prediction models of WT FBN1 and p.Y2588* mutated FBN1. The p.Y2588* mutation leads to the substitution of the 2588th amino acid of the wild-type FBN1 protein with a premature stop codon, resulting in an FBN1 protein with only 2588 amino acids, thereby lacking 283 amino acids. (D). Structural models for the wild-type and mutant FBN1 proteins in 2487aa-2686aa region. The p.Y2588* variant also led to a more loosely arranged and structurally abnormal conformation in the 2487aa-2588aa region of the protein, prior to the premature termination