Analysis of the Impact of Known SPINK1 Missense Variants on Pre-mRNA Splicing and/or mRNA Stability in a Full-Length Gene Assay

• Main Authors: Hao Wu, Arnaud Boulling, David N. Cooper, Zhao-Shen Li, Zhuan Liao, Claude Férec, Jian-Min Chen
• Format: Article
• Language: English
• Published: MDPI AG 2017-10-01
• Series: Genes
• Subjects: chronic pancreatitis; full-length gene assay; minigene assay; missense variant; mRNA stability; pre-mRNA splicing; SPINK1 gene
• Online Access: https://www.mdpi.com/2073-4425/8/10/263

It is increasingly appreciated that missense variants may not only alter protein structure and function but may also influence pre-mRNA splicing and/or mRNA stability. Here we explore this issue in the context of currently known SPINK1 missense variants using a full-length gene assay. We demonstrated that 4 (17%) out of 24 variants tested significantly reduced pre-mRNA splicing and/or stability as compared with the wild-type. However, since the strongest effect observed was a 23% reduction from normal, the contribution of SPINK1 missense variants to the clinical phenotype through an impact on mRNA processing alone may be relatively minor compared with their effects in relation to protein structure/function.