Fan Xin, Zhao Sen, Yu Chenxi, Wu Di, Yan Zihui, Fan Lijun, Song Yanning, Wang Yi, Li Chuan, Ming Yue, Gui Baoheng, Niu Yuchen, Li Xiaoxin, Yang Xinzhuang, Luo Shiyu, Zhang Qiang, Zhao Xiuli, Pan Hui, Li Mei, Xia Weibo, Qiu Guixing, Liu Pengfei, Zhang Shuyang, Zhang Jianguo, Wu Zhihong, Lupski James R, Posey Jennifer E, Chen Shaoke, Gong Chunxiu, Wu Nan
Department of Pediatrics, The Second Affiliated Hospital of Guangxi Medical University, Guangxi 530003, China.
Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China; Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing 100730, China.
J Genet Genomics. 2021 May 20;48(5):396-402. doi: 10.1016/j.jgg.2021.02.008. Epub 2021 Mar 22.
Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations. Although the diagnostic utility of clinical genetic testing in short stature has been implicated, the genetic architecture and the utility of genomic studies such as exome sequencing (ES) in a sizable cohort of patients with short stature have not been investigated systematically. In this study, we recruited 561 individuals with short stature from two centers in China during a 4-year period. We performed ES for all patients and available parents. All patients were retrospectively divided into two groups: an isolated short stature group (group I, n = 257) and an apparently syndromic short stature group (group II, n = 304). Causal variants were identified in 135 of 561 (24.1%) patients. In group I, 29 of 257 (11.3%) of the patients were solved by variants in 24 genes. In group II, 106 of 304 (34.9%) patients were solved by variants in 57 genes. Genes involved in fundamental cellular process played an important role in the genetic architecture of syndromic short stature. Distinct genetic architectures and pathophysiological processes underlie isolated and syndromic short stature.
身材矮小是儿童期最常见的内分泌疾病表型之一，可能单独出现或伴有其他临床表现。尽管临床基因检测在身材矮小诊断中的作用已得到关注，但身材矮小患者群体中基因结构以及外显子组测序（ES）等基因组研究的效用尚未得到系统研究。在本研究中，我们在4年期间从中国两个中心招募了561名身材矮小个体。我们对所有患者及其可获得的父母进行了外显子组测序。所有患者均被回顾性分为两组：单纯性身材矮小组（I组，n = 257）和明显综合征性身材矮小组（II组，n = 304）。在561名患者中的135名（24.1%）中鉴定出致病变异。在I组中，257名患者中的29名（11.3%）通过24个基因中的变异得到诊断。在II组中，304名患者中的106名（34.9%）通过57个基因中的变异得到诊断。参与基本细胞过程的基因在综合征性身材矮小的基因结构中起重要作用。单纯性和综合征性身材矮小有着不同的基因结构和病理生理过程。
