PMC6190816_01
Sequence electropherogram of the 2242+1G>T variant. Blue, dCTP; green, dATP; black, dGTP; red, dTTP.. Abbreviations: dATP, deoxyadenosine triphosphate; dCTP, deoxycytidine triphosphate; dGTP, deoxyguanosine triphosphate; DPYD, dihydropyrimidine dehydrogenase; dTTP, deoxythymidine triphosphate.
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We identified two variants in DPYD exons, c.1601G>A (rs1801158, p.Ser534Asn, DPYD*4) and a previously unreported splice site mutation at position 2242+1G>T, after the end of exon 19 (Figure 1).
Exon skipping sequence.. Notes: Left: Electrophoresis of amplified cDNA from peripheral blood mononuclear cells of a patient carrying the 2242+1G>T variant. Right, upper: Graphic representation of skipping of exon 19. Right, lower: Sequence electropherogram using the primer Ex18F. A double sequence is observed for 85 nucleotides corresponding to overlapping of exons 19 and 20.
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DPYD in the patient's mRNA (Figure 2). DPYD generated a truncated protein of 795 amino acids lacking the correct sequence from 767 to the end (1025) (Figure 3).
Structures of wild-type DPYD and truncated DPYD.. Notes: The interpretation of mutation effect and the molecular modeling were performed by using Deep View Swiss-PDB viewer and Tasser. (A) Modeling of wild-type DPYD; (B) modeling of truncated DPYD.
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DPYD in the patient's mRNA (Figure 2). DPYD generated a truncated protein of 795 amino acids lacking the correct sequence from 767 to the end (1025) (Figure 3).