Shen Yang, Zhang Lei, Chen Bosong, Dong Liangchao, Wang Yicheng, Wang Sun
Department of Orthopedics, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
The First Maternity and Infant Hospital Affiliated to Tongji University, Shanghai, China.
Transl Pediatr. 2020 Oct;9(5):619-628. doi: 10.21037/tp-20-191.
Hereditary multiple exostoses (HME), a rare genetic pediatric disorder, has a peculiar pathogenic mechanism. The results of previous studies have shown that HME is associated with mutations of the and genes at a molecular genetics level. In our study, two families who received therapy in the Department of Orthopedics of Shanghai Children's Hospital between June, 2017 and November, 2018 were recruited, and a mutational analysis of the genes was conducted to further elucidating the relationship between HME and .
Venous blood samples were collected from individuals with HME and their families. Exon sequencing and RT-PCR were performed to comprehensively analyze 11 exons of the gene.
The deletion of exon 7 and the 2397 G>T mutation in exon 7 caused deletion mutation and nonsense mutation only in the HME patients. The mutations in exon 7 were tested and verified by Sanger sequencing. RT-PCR showed that the mRNA expression of was significantly decreased in the mutation samples compared with the normal samples, which exerted a great influence on the function of .
This study identified new mutation sites for the pathogenesis of HME and further clarified the relationship between HME and .
遗传性多发性骨软骨瘤（HME）是一种罕见的儿童遗传性疾病，具有独特的致病机制。以往研究结果表明，在分子遗传学水平上，HME与 和 基因的突变有关。在我们的研究中，招募了2017年6月至2018年11月期间在上海儿童医学中心骨科接受治疗的两个家庭，并对 基因进行突变分析，以进一步阐明HME与 之间的关系。
采集HME患者及其家属的静脉血样本。进行外显子测序和RT-PCR，以全面分析 基因的11个外显子。
外显子7的缺失以及外显子7中的2397 G>T突变仅在HME患者中导致缺失突变和无义突变。通过桑格测序对外显子7中的突变进行了检测和验证。RT-PCR显示，与正常样本相比，突变样本中 的mRNA表达显著降低，这对 的功能产生了很大影响。
本研究确定了HME发病机制的新突变位点，并进一步阐明了HME与 之间的关系。
