Alternative splicing in a presenilin 2 variant associated with Alzheimer disease.
Jacquelyn E BragginStephanie A BucksMeredith M CourseCarole L SmithBryce SopherLeah OsnisKiel D ShueyKimiko Domoto-ReillyChristina CasoChizuru KinoshitaKathryn P ScherpelzChloe CrossThomas GrabowskiSeyyed H M NikMorgan NewmanGwenn A GardenJames B LeverenzDebby TsuangCaitlin LatimerLuis Francisco Gonzalez-CuyarChristopher Dirk KeeneRichard S MorrisonKristoffer RhoadsEllen M WijsmanMichael O DorschnerMichael LardelliJessica E YoungPaul N ValdmanisThomas D BirdSuman JayadevPublished in: Annals of clinical and translational neurology (2019)
These data suggest that PSEN2 K115Efs*11 is a likely pathogenic variant associated with AD. We uncovered novel PSEN2 alternative transcripts in addition to previously reported PSEN2 splice isoforms associated with sporadic AD. In the context of a frameshift, these alternative transcripts return to the canonical reading frame with potential to generate deleterious protein products. Our findings suggest novel potential mechanisms by which PSEN variants may influence AD pathogenesis, highlighting the complexity underlying genetic contribution to disease risk.