Guo Xiaoyan, Zheng Qinqin, Lin Mingrui, Zhang Yiyuan, Shi Tengfei
Department of Laboratory Medicine, Fuzhou Second Hospital Affiliated to Xiamen University, Fuzhou, Fujian 350007, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Jun 10;38(6):549-552. doi: 10.3760/cma.j.cn511374-20200415-00272.
To explore the genetic basis for a pedigree affected with hereditary multiple osteochondroma (HMO).
Peripheral blood samples were collected from the proband and members of his pedigree with informed consent. Following extraction of genomic DNA, all coding exons and flanking intronic sequences (-10 bp) of the EXT1 and EXT2 genes were subjected to targeted capture and next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing.
A heterozygous nonsense variant (c.1911C>A) was found in exon 10 of the EXT1 gene in the proband and his affected father but not in a healthy sister and normal controls. The variant was classified as a pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (PVS1+PM2+PP1). Bioinformatic analysis predicted that the c.1911C>A variant may be disease-causing via nonsense-mediated mRNA decay and anomalous splicing.
The c.1911C>A variant probably underlay the disease in this pedigree. Discovery of this variant enriched the variant spectrum of HMO.
探究一个遗传性多发性骨软骨瘤（HMO）家系的遗传基础。
在获得知情同意后，采集了先证者及其家系成员的外周血样本。提取基因组DNA后，对EXT1和EXT2基因的所有编码外显子及其侧翼内含子序列（-10 bp）进行靶向捕获和二代测序（NGS）。通过Sanger测序验证可疑变异。
在先证者及其患病父亲的EXT1基因第10外显子中发现了一个杂合无义变异（c.1911C>A），而在其健康姐姐和正常对照中未发现。根据美国医学遗传学与基因组学学会的指南（PVS1+PM2+PP1），该变异被分类为致病性变异。生物信息学分析预测，c.1911C>A变异可能通过无义介导的mRNA降解和异常剪接导致疾病。
c.1911C>A变异可能是该家系疾病的病因。该变异的发现丰富了HMO的变异谱。
