Analysis of the Impact of Known SPINK1 Missense Variants on Pre-mRNA Splicing and/or mRNA Stability in a Full-Length Gene Assay
Department of Gastroenterology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China
Institut National de la Santé et de la Recherche Médicale (INSERM), U1078, Brest 29238, France
Etablissement Français du Sang (EFS)—Bretagne, Brest 29200, France
Shanghai Institute of Pancreatic Diseases, Shanghai 200433, China
Institute of Medical Genetics, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK
Faculté de Médecine et des Sciences de la Santé, Université de Bretagne Occidentale (UBO), Brest 29238, France
Laboratoire de Génétique Moléculaire et d’Histocompatibilité, Centre Hospitalier Universitaire (CHU) Brest, Hôpital Morvan, Brest 29200, France
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Genes 2017, 8(10), 263; https://0-doi-org.brum.beds.ac.uk/10.3390/genes8100263
Received: 17 August 2017 / Revised: 25 September 2017 / Accepted: 6 October 2017 / Published: 10 October 2017
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.