{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T14:48:56Z","timestamp":1760453336507,"version":"build-2065373602"},"reference-count":50,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015777","name":"Division of Research Capacity Development","doi-asserted-by":"publisher","award":["HDID8682\/MB2022"],"award-info":[{"award-number":["HDID8682\/MB2022"]}],"id":[{"id":"10.13039\/501100015777","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Poikiloderma with tendon contracture, myopathy and pulmonary fibrosis (POIKTMP) is a rare hereditary disorder caused by mutations in the <jats:italic>FAM111B<\/jats:italic> gene, characterised by multi\u2010organ fibrosis, particularly affecting the lungs. This study investigates the molecular mechanisms of fibrosis in POIKTMP through genotyping and gene expression profiling of <jats:italic>FAM111B<\/jats:italic> and associated fibrotic pathways. Post\u2010mortem formalin\u2010fixed paraffin\u2010embedded (FFPE) tissues from a POIKTMP patient and healthy controls were analysed. Genomic DNA was extracted, confirming the <jats:italic>FAM111B Y621D<\/jats:italic> mutation via Sanger sequencing. RT\u2010qPCR and the RT<jats:sup>2<\/jats:sup> Profiler PCR Array were used to evaluate fibrosis\u2010related gene expression in lung and skin tissues. Disease and pathway enrichment analyses were conducted using Metascape, GeneMANIA and Enrichr tools. The <jats:italic>FAM111B Y621D<\/jats:italic> mutation was validated, and gene expression profiling revealed significant upregulation of fibrotic markers, such as <jats:italic>TGF\u03b2\u20103, PDGFA, ITGB1, MMP3, MMP13<\/jats:italic> and <jats:italic>CCN2<\/jats:italic> in the lungs, and <jats:italic>COL3A1<\/jats:italic> and <jats:italic>THBS2<\/jats:italic> in the skin. Pathway enrichment analysis linked FAM111B to extracellular matrix remodelling, cell adhesion, and cancer. These findings suggest that <jats:italic>FAM111B<\/jats:italic> mutations drive fibrosis through dysregulated gene networks, highlighting potential therapeutic targets for POIKTMP and related fibrotic diseases. Further research is required to understand <jats:italic>FAM111B<\/jats:italic>'s role in fibrosis fully.<\/jats:p>","DOI":"10.1111\/jcmm.70871","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T03:41:26Z","timestamp":1759808486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Integrative Genotyping and Gene Expression Profiling of the Mutated Human <i>FAM111B<\/i> Gene and Fibrosis\u2010Associated Pathway in the POIKTMP Syndrome"],"prefix":"10.1111","volume":"29","author":[{"given":"Nadine","family":"Tambwe","sequence":"first","affiliation":[{"name":"Hair and Skin Research Lab, Division of Dermatology, Department of Medicine University of Cape Town  Cape Town South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Musalula","family":"Sinkala","sequence":"additional","affiliation":[{"name":"Division of Computational Biology, Department of Integrative 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