一个遗传性牙本质发育不全Ⅱ型家系的临床及遗传学分析

Clinical and genetic analysis of a pedigree affected with hereditary dentinogenesis imperfecta type Ⅱ

目的探讨一个遗传性牙本质发育不全(dentinogenesis imperfecta,DGI)Ⅱ型家系的临床表型和遗传学特点,明确其致病原因,并为遗传咨询提供依据。方法收集先证者及其家系成员的临床资料,采集外周血样,提取全基因组DNA,通过全外显子组测序检测潜在的致病变异位点。结果该家系患病成员表现为患牙呈琥珀色半透明状、球状牙冠、牙颈短缩、牙齿磨耗、髓腔及根管闭锁,与DGI-Ⅱ型相符,其牙本质涎磷蛋白(dentin sialophosphoprotein,DSPP)基因第5外显子均存在c.2837delA(p.Asp946Valfs*368)杂合移码变异,未见文献报道和数据库收录,根据美国医学遗传学与基因组学学会指南评级为疑似致病变异(PVS1_Strong+PM2)。结论DSPP基因第5外显子c.2837delA(p.Asp946Valfs*368)杂合移码变异可能是该家系的致病原因。上述发现丰富了DSPP基因的变异谱,为该家系的分子诊断和遗传咨询提供了依据。

Objective To explore the clinical and genetic characteristics of a Chinese pedigree affected with hereditary dentinogenesis imperfecta(DGI)typeⅡ.Methods Clinical data of the pedigree members were collected.Genomic DNA was extracted from peripheral blood samples and subjected to whole exome sequencing.Results Clinical characteristics of the affected family members have included amber teeth along with significant attrition,constricted roots and dentine hypertrophy leading to pulpal obliteration,which were suggestive of DGI typeⅡ.All of the affected members were found to have harbored a novel heterozygous c.2837delA(p.Asp946Valfs*368)variant of the DSPP gene which was predicted to be likely pathogenic.Conclusion The c.2837delA variant of the DSPP gene probably underlay the disease in this pedigree.Above finding has expanded the variant spectrum of DSPP gene and provided a basis for molecular diagnosis and genetic counseling for this pedigree.