Differential gene expression profile of germline STK11 deletion in patient derived fibroblasts

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder hallmarked by mucocutaneous melanocytic macules and gastrointestinal hamartomatous polyposis associated with germline/somatic pathogenic variants in the tumor suppressor STK11. PJS is clinically heterogeneous, however, the relationship between clinical phenotype and genotype remains elusive. Here, we report a family with variable severity PJS who harbor a heterozygous STK11 whole gene deletion combined with heterozygous variants in PMS2 and TP53AIP1 that segregate with disease severity in the family. RNA-seq analysis followed by qRT-PCR confirmed that expression of STK11, TP53, PMS2, and TP53AIP1 and a large fraction of p53 signaling pathway components, are significantly reduced while Wnt signaling pathway effectors are upregulated in cells from an individual with severe disease To investigate the differnetial gene expression profiles in patient dernmal fibroblasts compared to control fibroblasts