Sequence changes in predicted promoter elements of STK11/LKB1 are unlikely to contribute to Peutz-Jeghers syndrome

Abstract

Background: Germline mutations or large-scale deletions in the coding region and splice sites of STK11/LKB1 do not account for all cases of Peutz-Jeghers syndrome (PJS). It is conceivable that, on the basis of data from other diseases, inherited variation in promoter elements of STK11/LKB1 may cause PJS.

Results: Phylogenetic foot printing and transcription factor binding site prediction of sequence 5' to the coding sequence of STK11/LKB1 was performed to identify non-coding sequences of DNA indicative of regulatory elements. A series of 33 PJS cases in whom no mutation in STK11/LKB1 could be identified were screened for sequence changes in the putative promoter defined by nucleotides -1090 to -1472. Two novel sequence changes were identified, but were found to be present in healthy individuals.

Conclusion: These findings indicate that promoter sequence changes are unlikely to contribute to PJS.

Figure 1

in-silico identification of the putative STK11/LKB1 promoter. (a) ECR browser output. Regions of high sequence conservation 5' of STK11 exon 1 are annotated with transcription factor binding sites as predicted by rVista v2.0 between nucleotides -981 to -1668. (c) ConSite output. Sequence of high conservation is annotated with predicted transcription factor binding sites (TFBS) as predicted by the JASPER TFBS database between nucleotides -1104 to -1613. (b) Ideogram showing consensus conserved region, defined at the 3' end by the E74A TFBS predicted ConSite, and at the 5' end by the CMYB TFBS predicted by rVista. Arrows indicate the genomic sequence analysed.