{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:00:07Z","timestamp":1777658407532,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":226,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>Peutz\u2013Jeghers 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 <jats:italic>STK11<\/jats:italic>. PJS is clinically heterogeneous; however, the relationship between clinical phenotype and genotype remains elusive. Here, we report a family with PJS that harbors a heterozygous <jats:italic>STK11<\/jats:italic> whole gene deletion combined with a heterozygous variant in <jats:italic>TP53AIP1<\/jats:italic> that segregates with mucocutaneous pigmentation in the family. RNA\u2010seq analysis followed by qRT\u2010PCR confirmed that the expression of <jats:italic>STK11<\/jats:italic>, <jats:italic>TP53<\/jats:italic>, and <jats:italic>TP53AIP1<\/jats:italic> and a large fraction of p53 signaling pathway components are significantly reduced, while Wnt signaling pathway effectors are upregulated in cells from an affected individual. Our findings shed light on transcriptome\u2010level pathway dysregulation in PJS with germline deletion of <jats:italic>STK11<\/jats:italic>. Further evaluation of mutational burden across relevant signaling pathways can likely inform disease prognosis.<\/jats:p>","DOI":"10.1155\/humu\/5530710","type":"journal-article","created":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T05:35:11Z","timestamp":1755322511000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic Investigation and Transcriptome Profiling in a Nuclear Family With Peutz\u2013Jeghers Syndrome"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3096-8795","authenticated-orcid":false,"given":"Tahir N.","family":"Khan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4496-5464","authenticated-orcid":false,"given":"Kai 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