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目的:对1个遗传性多发性骨软骨瘤家系进行基因变异检测，明确其可能的致病原因。方法:提取先证者及其家系成员的外周血基因组DNA，用二代测序技术(next generation sequencing，NGS)筛查先证者n EXT1/n EXT2编码区及邻近内含子序列，对疑似致病变异进行先证者及家系成员Sanger测序和酶切验证。n 结果:NGS检测结果显示先证者n EXT1基因第10外显子存在c.1911C>A杂合无义变异，Sanger测序验证家系中先证者及父亲均检测到该变异，而先证者三姐及对照均未携带该变异。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南，判定n EXT1基因c.1911C>A变异为致病性变异(PVS1+PM2+PP1)。n 结论:EXT1基因的c.1911C>A可能是该家系的致病原因，该变异的检出拓展了遗传性多发性骨软骨瘤的基因变异谱。n “,”Objective:To explore the genetic basis for a pedigree affected with hereditary multiple osteochondroma (HMO).Methods: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 n EXT1 and n EXT2 genes were subjected to targeted capture and next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing.n Results:A heterozygous nonsense variant (c.1911C>A) was found in exon 10 of then 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.n Conclusion:The c. 1911C>A variant probably underlay the disease in this pedigree. Discovery of this variant enriched the variant spectrum of HMO.