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目的:对1例表现为骨骼和牙齿矿化不全、乳牙早脱、佝偻病、身材矮小女性患儿的n ALPL基因进行变异分析，明确其可能的遗传学病因。n 方法:采集患儿及其正常表型亲代外周血样，提取基因组DNA，应用高通量测序技术进行变异检测，对疑似致病变异进行Sanger测序、家系分析和生物信息学分析。结果:测序结果显示患儿的n ALPL基因第10外显子存在c.1130C>T(p.Ala377Val)和第11外显子c.1300G>A(p.Val434Met)复合杂合变异，其中c.1130C>T(p.Ala377Val)遗传自父亲，为已报道的致病变异，c.1300G>A(p.Val434Met)遗传自母亲，尚未见文献报道，生物信息分析软件预测有害，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评级为可能致病(PM2+PM5+PP3+PP4)。n 结论:ALPL基因第10外显子c.1130C>T(p.Ala377Val)和第11外显子c.1300G>A(p.Val434Met)复合杂合变异可能是患儿的致病原因，新变异的发现丰富了n ALPL基因变异谱。n “,”Objective:To explore the genetic basis for a girl featuring bone and tooth mineralization disorder, premature deciduous teeth, rickets and short stature.Methods:Genomic DNA was extracted and subjected to high-throughput whole exome sequencing. Suspected variants were confirmed by Sanger sequencing. Impact of potential variants was analyzed with bioinformatic software.Results:The child was found to carry compound heterozygous missense variants of the n ALPL gene, including c. 1130C>T (p.A377V), a known pathogenic mutation inherited from her father, and c. 1300G>A (p.V434M) inherited from her mother, which was unreported previously and predicted to be likely pathogenic based on standards and guidelines from the American College of Medical Genetics and Genomics (PM2+ PM5+ PP3+ PP4).n Conclusion:The compound heterozygous variants of c. 1130C>T (p.Ala377Val) and c. 1300G>A (p.Val434Met) of then ALPL gene probably underlay the disease in this child. Above finding has enriched the spectrum of n ALPL gene variants.n