Impact of WFS1 alternative splicing variants on beta cell apoptosis in a patient with Wolfram Syndrome.

The goal is to uncover the alternative splicing of WFS1 mRNA occurring in a pediatric patient harboring a mutation in the acceptor splice site (ASS) of exon 4 of the WFS1 gene. We further evaluated the impact of accumulation of the PTC-carrying WFS1 alternative transcripts in pancreatic beta cells upon exogenous stress and/or inflammation. Molecular analysis of transcipional landscape originating from disruption of aforemontioned canonical ASS in the WFS1 gene was performed of patient-derived induced pluripotent stem cells, following in vitro differentiation into insulin-producing pancreatic beta cells.