Novel GZF1 pathogenic variants identified in two Chinese patients with Larsen syndrome.
Novel GZF1 pathogenic variants identified in two Chinese patients with Larsen syndrome.
复制标题
在两名中国拉森综合征患者中发现新的 GZF1 致病变异。
DOI：
10.1111/cge.13856
复制
发表时间：
2020
影响因子：
3.5
通讯作者：
Wu Lingqian
中科院分区：
文献类型：
--
作者：
Zeng Lanlan;Li Zhibin;Pan Lijuan;Li Hongyan;Wu Jiayu;Yuan Xiying;Li Zhuo;Liang Desheng;Wu Lingqian
GZF 1最近被报道为与Larsen综合征相关的遗传因子。通过全外显子组测序，发现两名髋关节脱位、脊柱侧凸和严重近视以及听力损失和其他异常特征的患者携带两种新型GZF 1复合杂合变体（c.397400del，p. Leu 133 fs;和c.1474del，p. Met 492 fs）。L133 fs-GZF 1的mRNA表达水平与WT-GZF 1无显著差异。然而，通过蛋白质印迹法未检测到HA缀合的突变蛋白，这也通过免疫荧光染色证实。此外，M492 fs ‐ GZF 1的mRNA转录和蛋白表达水平均显著低于野生型，HA标记的M492 fs ‐ GZF 1主要分布于HEK 293 T细胞的胞浆中。这些结果表明，这两种变异体可能导致GZF 1功能丧失。我们的研究是第二个报道GZF 1变异体与Larsen综合征相关的研究。我们还为GZF 1变异体的致病性提供了功能证据，这扩大了突变谱，为GZF 1在Larsen综合征发病中的作用的功能研究提供了基础。
GZF1 was recently reported as a genetic factor associated with Larsen syndrome. Two patients presenting hip dislocation, scoliosis and severe myopia, as well as hearing loss and other abnormal features, were found to carry two novel compounds heterozygous variants inGZF1(c.397400del, p. Leu133fs; and c.1474del, p. Met492fs) through whole‐exome sequencing. The mRNA expression level of L133fs‐GZF1did not significantly differ from that of WT‐GZF1. However, no HA‐conjugated mutant protein was detected by western blotting, which was also confirmed by immunofluorescence staining. In addition, both mRNA transcription and protein expression levels of M492fs‐GZF1were significantly lower than those of wild type, and HA‐tagged M492fs‐GZF1 was mainly distributed in the cytoplasm of HEK 293 T cells. These results suggested that the two variants could lead to loss of function ofGZF1. Our study was the second to report the association betweenGZF1variants and Larsen syndrome. We also provided functional evidence for the pathogenicity ofGZF1variants, which expands the mutation spectrum and offers a basis for functional research on the role ofGZF1in the development of Larsen syndrome.