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目的:对1例颅锁骨发育不全(cleidocranial dysplasia, CCD)患儿n RUNX2基因进行变异分析，明确其可能的致病原因。n 方法:收集患儿及其父母外周血，提取基因组DNA，应用全外显子测序对患儿进行检测，并用Sanger测序对先证者及父母进行验证。结果:全外显子测序检测到患儿n RUNX2基因发生了c.460G>T(p.Val154Phe)错义变异(GRCh37/hg19)，该变异位于Runt结构域，高度保守(PM1)，在正常人群数据库频率为0(PM2)，多种计算机软件预测有害(PP3)，与患者临床表型高度相符(PP4)。该变异为未报道过的新变异；Sanger测序验证显示患儿父母均未检测到该变异，因此患儿的变异为新发变异(PS2)，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，n RUNX2基因c.460G>T变异判定为致病性变异(PS2+PM1+PM2+PP3+PP4)。n 结论:RUNX2基因c.460G>T(p.Val154Phe)变异可能为患儿的致病原因，新变异的检出扩展了n RUNX2基因变异谱。n “,”Objective:To explore the genetic basis for a Chinese patient featuring cleidocranial dysplasia(CCD).Methods:Genomic DNA was extracted from peripheral blood samples of the patient and his parents. Whole exome sequencing (WES) was carried out for the patient, and suspected variant was verified by Sanger sequencing.Results:WES has identified a missense c. 460G>T (p.Val154Phe) (GRCh37/hg19)variant of then RUNX2 gene. The variant was located in the Runt domain, a highly conserved region (PM1); it was not present in either the Genome Aggregation Database or the 1000 Genomes Project (PM2), and was predicted to have a deleterious effect on the gene product by multiple n in silico prediction tools (PP3); the clinical phenotype of the patient was highly consistent with that of cleidocranial dysplasia (PP4). Furthermore, the variant was unreported in medical literature and was absent in both parents (PS2). Based on the American College of Medical Genetics and Genomics guidelines, the c. 460G>T variant ofn RUNX2 gene was predicted to be pathogenic(PS2+ PM1+ PM2+ PP3+ PP4).n Conclusion:The c. 460G>T (p.Val154Phe) variant of then RUNX2 gene probably underlay the clinical phenotype in the patient. Above finding has enabled accurate diagnosis and expanded the spectrum of n RUNX2 variants.n