biostudies-literatureStasek SDFGziaf083https://www.ebi.ac.uk/biostudies/studies/S-EPMC12202044biostudies-literatureUnknown9(7)OI is a genetically diverse disorder characterized by bone fragility and deformities, with most cases attributed to dominant mutations in collagen I-related genes. However, mutations in <i>TENT5A</i>, encoding a poly(A) polymerase, have recently been implicated in severe, recessive forms of OI. We reported 3 individuals from a consanguineous family with a novel homozygous <i>TENT5A</i> variant (c.672G>T, p.Arg224Ser). Our patients presented with severe bone fragility, generalized osteopenia, skeletal deformities, short stature, and early wheelchair dependence. Patient-derived fibroblasts demonstrated impaired collagen secretion and disorganized fibril network formation. Our findings provide new insights into the complex pathophysiology of <i>TENT5A</i>-associated OI and underscore the needJBMR plusTENT5A-associated osteogenesis imperfecta: long-term follow-up and molecular insights.PMC12202044ZA 561/3-2407168728ET144/3-2 - 384170921384170921SE2373/1-2Stasek SReincke SRehberg MBaumann USemler OZaucke FMorgelin MHoyer-Kuhn HStephan AEtich JfalseTENT5A-associated osteogenesis imperfecta: long-term follow-up and molecular insights.OI is a genetically diverse disorder characterized by bone fragility and deformities, with most cases attributed to dominant mutations in collagen I-related genes. However, mutations in <i>TENT5A</i>, encoding a poly(A) polymerase, have recently been implicated in severe, recessive forms of OI. We reported 3 individuals from a consanguineous family with a novel homozygous <i>TENT5A</i> variant (c.672G>T, p.Arg224Ser). Our patients presented with severe bone fragility, generalized osteopenia, skeletal deformities, short stature, and early wheelchair dependence. Patient-derived fibroblasts demonstrated impaired collagen secretion and disorganized fibril network formation. Our findings provide new insights into the complex pathophysiology of <i>TENT5A</i>-associated OI and underscore the need2025-01-01T00:00:00Z2025 Jul2026-06-02T08:54:27.189Z2026-04-16T03:12:49.488ZS-EPMC122020444057545510.1093/jbmrpl/ziaf083