Stasek Stefanie, Zaucke Frank, Stephan Alice, Etich Julia, Mörgelin Matthias, Baumann Ulrich, Rehberg Mirko, Reincke Susanna, Semler Oliver, Hoyer-Kuhn Heike
Department of Pediatric and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany.
Dr. Rolf M. Schwiete Research Unit for Osteoarthritis, Department of Trauma Surgery and Orthopedics, University Hospital, Goethe University Frankfurt, 60590 Frankfurt/Main, Germany.
JBMR Plus. 2025 May 11;9(7):ziaf083. doi: 10.1093/jbmrpl/ziaf083. eCollection 2025 Jul.
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 , 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 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 -associated OI and underscore the need for further research into its role in skeletal homeostasis.
成骨不全症（OI）是一种具有遗传多样性的疾病，其特征为骨骼脆弱和畸形，大多数病例归因于I型胶原蛋白相关基因的显性突变。然而，编码聚腺苷酸聚合酶的基因发生突变，最近被认为与严重的隐性成骨不全症有关。我们报告了来自一个近亲家庭的3名个体，他们携带一种新的纯合变异（c.672G>T，p.Arg224Ser）。我们的患者表现出严重的骨骼脆弱、全身性骨质减少、骨骼畸形、身材矮小以及早期依赖轮椅。患者来源的成纤维细胞显示胶原蛋白分泌受损和原纤维网络形成紊乱。我们的研究结果为与该基因相关的成骨不全症的复杂病理生理学提供了新的见解，并强调有必要进一步研究其在骨骼稳态中的作用。
