TENT5A-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 TENT5A, 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 TENT5A 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 TENT5A-associated OI and underscore the need for further research into its role in skeletal homeostasis.