Fusion of FIP1L1 to PDGFRA involves the use of cryptic splice sites. (A) Splicing of exon 11 to exon 12 as it occurs in wild-type PDGFRA. (B) Splicing of FIP1L1 exons to the truncated exon 12 of PDGFRA as observed in 2 different HES patients. As the normal splice site in front of exon 12 is deleted, cryptic splice sites in the introns of FIP1L1 (as in case a) or within exon 12 (as in case b) are used to generate in-frame FIP1L1-PDGFRA fusions. As a result, the fusion protein sometimes contains a few extra amino acids derived from an intronic sequence of FIP1L1 (as in case a). Sequences from FIP1L1 are shown in lowercase letters and in gray; PDGFRA sequences are shown in capital letters and in black. Introns are depicted as lines; exons are shown as blocks. Splice sites are underlined in the sequence. The spliced RNA sequence and corresponding protein sequence are shown under the DNA. Cryptic splice sites are indicated with an arrow. Arrowheads indicate where the breakpoints are located in exon 12 of PDGFRA in cases a and b.