目的:对1个色素异常性皮肤淀粉样变性家系的3例患者的n GPNMB基因进行变异分析，明确其致病原因。n 方法:对先证者行高通量测序，采用生物信息学方法寻找致病基因变异，并通过Sanger测序对家系内成员是否携带变异进行验证。结果:先证者及其哥哥、妹妹n GPNMB基因的第5外显子均存在c.565C>T(p.Arg189X)纯合无义变异，其变异后蛋白发生截短进而蛋白功能丧失。父亲携带c.565C>T(p.Arg189X)杂合变异，母亲因死亡无法验证。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，c.565C>T变异为可能致病性变异(PS3＋PM2＋PP1＋PP3)。n 结论:GPNMB基因第5外显子c.565C>T(p.Arg189X)纯合变异可能为该色素异常性皮肤淀粉样变性家系患者的致病原因，新变异的检出拓宽了n GPNMB基因的变异谱。n “,”Objective:To explore the genetic basis for a Chinese pedigree affected with amyloidosis cutis dyschromica.Methods:High throughput sequencing was carried out for the proband.Bioinformatic analysis was used to identify the pathogenic variants.The result was verified by Sanger sequencing.Results:A homozygous nonsense variant c. 565C>T (p.Arg189X) of then GPNMB gene was identified in the proband, his elder brother and younger sister, which resulted a truncated protein with loss of function. The father of the proband was a heterozygous carrier. The genotype of his mother was unknown since she had passed away. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c. 565C>T variant was predicted to be likely pathogenic(PS3+ PM2+ PP1+ PP3).n Conclusion:The novel homozygous n GPNMB variant probably underlay the amyloidosis cutis dyschromica in this pedigree. Above finding has expanded the variant spectrum of the n GPNMB gene.n