Hereditary POIKTMP caused by FAM111B variants

Poikiloderma, hereditary fibrosing, with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is a rare genetic multisystemic fibrosing disorderdisease caused by heterozygous mutations in the FAM111B gene. To date, its molecular pathogenesis remains poorly defined. The FAM111B gene encodes a trypsin-like serine protease, primarily studied in the context of cancer. Intriguingly, the fact that germinal FAM111B variants do not consistently result in tumoral disorders suggests a broader functional scope for this protein that extends beyond its role in cell proliferation. This study comprehensively explored the global cellular landscape of POIKTMP patient cells carrying FAM111B missense variants using a multi-omics strategiy.