Costantini Alice, Muurinen Mari H, Mäkitie Outi
Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Folkhälsan Institute of Genetics, University of Helsinki, Helsinki, Finland.
Endocr Connect. 2021 May 10;10(5):R160-R174. doi: 10.1530/EC-21-0083.
In the last decade, the widespread use of massively parallel sequencing has considerably boosted the number of novel gene discoveries in monogenic skeletal diseases with short stature. Defects in genes playing a role in the maintenance and function of the growth plate, the site of longitudinal bone growth, are a well-known cause of skeletal diseases with short stature. However, several genes involved in extracellular matrix composition or maintenance as well as genes partaking in various biological processes have also been characterized. This review aims to describe the latest genetic findings in spondyloepiphyseal dysplasias, spondyloepimetaphyseal dysplasias, and some monogenic forms of isolated short stature. Some examples of novel genetic mechanisms leading to skeletal conditions with short stature will be described. Strategies on how to successfully characterize novel skeletal phenotypes with short stature and genetic approaches to detect and validate novel gene-disease correlations will be discussed in detail. In summary, we review the latest gene discoveries underlying skeletal diseases with short stature and emphasize the importance of characterizing novel molecular mechanisms for genetic counseling, for an optimal management of the disease, and for therapeutic innovations.
在过去十年中，大规模平行测序的广泛应用极大地增加了在伴有身材矮小的单基因骨骼疾病中发现新基因的数量。生长板是纵向骨生长的部位，在生长板维持和功能中起作用的基因缺陷是伴有身材矮小的骨骼疾病的一个众所周知的病因。然而，一些参与细胞外基质组成或维持的基因以及参与各种生物学过程的基因也已得到表征。本综述旨在描述脊椎骨骺发育不良、脊椎干骺端发育不良以及一些孤立性身材矮小的单基因形式的最新遗传学发现。将描述一些导致伴有身材矮小的骨骼疾病的新遗传机制的例子。将详细讨论如何成功表征伴有身材矮小的新骨骼表型的策略以及检测和验证新基因-疾病相关性的遗传方法。总之，我们综述了伴有身材矮小的骨骼疾病的最新基因发现，并强调表征新分子机制对于遗传咨询、疾病的最佳管理和治疗创新的重要性。
