Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Bone. 2022 Nov;164:116520. doi: 10.1016/j.bone.2022.116520. Epub 2022 Aug 15.
The clinical and radiological variability seen in different forms of osteopetrosis, all due to impaired osteoclastic bone resorption, reflect many causal genes. Both defective differentiation of osteoclasts from hematopoietic stem cells as well as disturbed functioning of osteoclasts can be the underlying pathogenic mechanism. Pathogenic variants in PLEKHM1 and SNX10 can be classified among the latter as they impair vesicular transport within the osteoclast and therefore result in the absence of a ruffled border. Some of the typical radiological hallmarks of osteopetrosis can be seen, and most cases present as a relatively mild form segregating in an autosomal recessive mode of inheritance.
不同形式的成骨不全症的临床和影像学表现均由于破骨细胞骨吸收受损所致，反映了许多致病基因。破骨细胞从造血干细胞分化缺陷以及破骨细胞功能紊乱均可作为潜在的发病机制。PLEKHM1 和 SNX10 的致病变异可归为后者，因为它们会损害破骨细胞内的小泡运输，从而导致皱襞边缘缺失。一些成骨不全症的典型影像学特征可见，大多数病例表现为常染色体隐性遗传模式下相对较轻的形式。
