一个先天性脊柱骨骺发育不良家系的COL2A1基因变异分析

摘要

目的 对1个先天性脊柱骨骺发育不良(spondyloepiphyseal dysplasia congenita,SEDC)家系进行基因检测和蛋白功能预测,探讨其致病原因.方法 对1个SEDC家系先证者行全外显子基因检测,对可疑基因变异进行Sanger测序验证,使用蛋白功能预测软件对可疑基因变异进行功能预测.结果 该SEDC家系中3例患者均携带COL2A1基因c.1394G>C(p.Gly465Ala)错义变异,该变异在目前常用数据库中均未见报道.PROVEAN、PolyPhen-2、Mutation Taster软件预测该变异为高度可能致病性变异.结论 COL2A1基因c.1394G>C(p.Gly465Ala)变异可能是该SEDC家系的致病原因.%Objective To explore the molecular basis for a pedigree affected with spondyloepiphyseal dysplasia congenita (SEDC).Methods The proband was subjected to whole exome sequencing.Suspected variant was verified by Sanger sequencing.Results All patients from the pedigree were found to carry a novel missense variant c.1394G > C (p.Gly465Ala)of the COL2A1 gene.The variant was not reported previously.Provean,Polyphen-2 and Mutation Taster software predicted that the variant is highly likely to be pathogenic.Conclusion The c.1394G > C (p.Gly465Ala)variant of the COL2A1 gene probably underlies the SEDC in this pedigree.