Kämpe Anders J, Mäkitie Riikka E, Mäkitie Outi
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Horm Res Paediatr. 2015;84(6):361-9. doi: 10.1159/000439566. Epub 2015 Oct 31.
Recent developments in genetic technology have given us the opportunity to look at diseases in a new and more detailed way. This Mini Review discusses monogenetic forms of childhood-onset primary osteoporosis, with the main focus on osteoporosis caused by mutations in WNT1 and PLS3, two of the most recently discovered genes underlying early-onset osteoporosis. The importance of WNT1 in the accrual and maintenance of bone mass through activation of canonical WNT signaling was recognized in 2013. WNT1 was shown to be a key ligand for the WNT-signaling pathway, which is of major importance in the regulation of bone formation. More recently, mutations in PLS3, located on the X chromosome, were shown to be the cause of X-linked childhood-onset primary osteoporosis affecting mainly males. The function of PLS3 in bone metabolism is still not completely understood, but it has been speculated to have an important role in mechanosensing by osteocytes and in matrix mineralization. In this new era of genetics, our knowledge on genetic causes of childhood-onset osteoporosis expands constantly. These discoveries bring new possibilities, but also new challenges. Guidelines are needed to implement this new genetic knowledge to clinical patient care and to guide genetic investigations in affected families.
基因技术的最新进展使我们有机会以一种全新且更详细的方式看待疾病。本综述讨论儿童期起病的原发性骨质疏松症的单基因形式，主要聚焦于由WNT1和PLS3突变引起的骨质疏松症，这是最近发现的两个早发性骨质疏松症相关基因。2013年，人们认识到WNT1通过激活经典WNT信号通路在骨量积累和维持中的重要性。WNT1被证明是WNT信号通路的关键配体，在骨形成调节中起主要作用。最近，位于X染色体上的PLS3突变被证明是主要影响男性的X连锁儿童期起病的原发性骨质疏松症的病因。PLS3在骨代谢中的功能仍未完全明确，但据推测它在骨细胞的机械传感和基质矿化中起重要作用。在这个遗传学的新时代，我们对儿童期起病骨质疏松症的遗传病因的认识在不断扩展。这些发现带来了新的可能性，但也带来了新的挑战。需要制定指南，将这些新的遗传学知识应用于临床患者护理，并指导对受影响家庭的基因研究。
