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 Overall design: To investigate the differnetial gene expression profiles in patient dernmal fibroblasts compared to control fibroblasts