先天性脊柱侧凸和青少年特发性脊柱侧凸中 的突变景观。
The Mutational Landscape of in Congenital Scoliosis and Adolescent Idiopathic Scoliosis.
机构信息
State Key Laboratory of Complex Severe and Rare Diseases, Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
Graduate School, Peking Union Medical College, Beijing 100005, China.
出版信息
Genes (Basel). 2021 Nov 12;12(11):1791. doi: 10.3390/genes12111791.
Depletion of is associated with both congenital scoliosis (CS) and adolescent idiopathic scoliosis (AIS) in zebrafish models. However, only one human variant of has been reported previously in a patient with AIS. In this study, we systemically investigated the variant landscape of in 583 patients with CS and 302 patients with AIS from the Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study. We identified a total of four rare variants in CS and four variants in AIS, including one protein truncating variant (c.464_465delAC) in a patient with CS. We then explored the effects of these variants on protein expression and sub-cellular location. We confirmed that the c.464_465delAC variant causes loss-of-function (LoF) of . In addition, the c.353C>T and c.2290G>A variants identified in two patients with AIS led to reduced protein expression of PTK7 as compared to that of the wild type. In conclusion, LoF and hypomorphic variants are associated with CS and AIS, respectively.
在斑马鱼模型中， 缺失与先天性脊柱侧凸 (CS) 和青少年特发性脊柱侧凸 (AIS) 都有关。然而，之前仅在一名 AIS 患者中报道过 基因的一个人类变异体。在这项研究中，我们系统性地研究了来自 Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) 研究的 583 名 CS 患者和 302 名 AIS 患者中 的变异景观。我们在 CS 中总共鉴定出了四个罕见变异体和四个 AIS 中的变异体，包括一名 CS 患者中的一个蛋白截断变异体 (c.464_465delAC)。然后，我们探索了这些变异对蛋白表达和亚细胞定位的影响。我们证实 c.464_465delAC 变异导致 基因功能丧失 (LoF)。此外，在两名 AIS 患者中鉴定出的 c.353C>T 和 c.2290G>A 变异导致与野生型相比，PTK7 蛋白表达减少。总之，功能丧失和低功能变体分别与 CS 和 AIS 相关。
Zotero 插件