4 years ago

In vitro and in silico evidence against a significant effect of the SPINK1 c.194G>A variant on pre-mRNA splicing

We read with interest the recent publication of Beer and Sahin-Tóth1 reporting that exonic variants affecting pre-mRNA splicing contribute to the genetic burden in chronic pancreatitis. One particular variant, affecting the last nucleotide of exon 3 of the SPINK1 gene, c.194G>A, was found to cause an ~80% reduction in SPINK1 mRNA expression as compared with the wild type in a minigene assay performed in human embryonic kidney 293T (HEK293T) cells. The SPINK1 sequence inserted into the minigene expression vector however comprised only exon 1, exon 2, exon 3, intron 3 and exon 4 of the four-exon gene.1 It should be noted that the potential effect of c.194G>A as a missense mutation (p.Arg65Gln) on protein function has previously been analysed; engineered expression of the full-length mutant coding sequence in Chinese hamster ovary cells and HEK293T cells showed a consistent 50%–60% reduction in protein secretion as compared...

Publisher URL: http://gut.bmj.com/cgi/content/short/66/12/2195

DOI: 10.1136/gutjnl-2017-313948

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