Humanitas Clinical and Research Institute, via Manzoni 113, 20089, Rozzano, MI, Italy.
Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy.
Curr Osteoporos Rep. 2018 Feb;16(1):13-25. doi: 10.1007/s11914-018-0415-2.
The term osteopetrosis refers to a group of rare skeletal diseases sharing the hallmark of a generalized increase in bone density owing to a defect in bone resorption. Osteopetrosis is clinically and genetically heterogeneous, and a precise molecular classification is relevant for prognosis and treatment. Here, we review recent data on the pathogenesis of this disorder.
Novel mutations in known genes as well as defects in new genes have been recently reported, further expanding the spectrum of molecular defects leading to osteopetrosis. Exploitation of next-generation sequencing tools is ever spreading, facilitating differential diagnosis. Some complex phenotypes in which osteopetrosis is accompanied by additional clinical features have received a molecular classification, also involving new genes. Moreover, novel types of mutations have been recognized, which for their nature or genomic location are at high risk being neglected. Yet, the causative mutation is unknown in some patients, indicating that the genetics of osteopetrosis still deserves intense research efforts.
成骨不全症是一组罕见的骨骼疾病，其特征为由于骨吸收缺陷导致骨密度普遍增加。成骨不全症在临床上和遗传上具有异质性，精确的分子分类与预后和治疗相关。在此，我们综述该疾病发病机制的最新数据。
新报告了一些已知基因中的新突变以及新基因中的缺陷，进一步扩大了导致成骨不全症的分子缺陷谱。下一代测序工具的应用不断扩展，有助于鉴别诊断。一些复杂的表型，其中成骨不全症伴有其他临床特征，也涉及新基因，进行了分子分类。此外，还认识到了新型突变，由于其性质或基因组位置，存在被忽视的高风险。然而，一些患者的致病突变仍然未知，表明成骨不全症的遗传学仍需要深入研究。
