目的:目的:通过收集中国人群中牙本质发育异常的多个家系,对疾病进行表型分析和分型诊断,筛查候选基因牙本质涎磷蛋白基因(DSPP)是否存在致病突变,进一步探讨基因突变与疾病表型的相关性.方法:收集牙本质发育异常的中国人家系,采集患者及家系成员外周静脉血样,提取基因组DNA,应用PCR方法扩增候选基因DSPP各外显子编码区及剪切位侧翼序列,产物进行DNA直接测序,利用BLAST、GENBANK进行序列分析,筛查可疑变异,并检索DSPP突变和多态数据库.结果:本研究共收集到3个牙本质发育不全(DGI)家系,其中一家系除具有DGI-Ⅱ的特征表型外,还伴有口干症表型.3个家系在牙本质涎蛋白(DSP)编码区均未发现突变,在其中2个DGI-Ⅱ家系发现牙本质磷蛋白(DPP)编码区一处共同的框移突变c.3546-3550delTAGCAinsG,与已报道的DPP突变相同.结论:本研究报道了牙本质发育异常的新表型,DPP编码区突变是引起中国人群DGI-Ⅱ的重要致病因素,DSPP c.3546-3550delTAGCAins突变可能是中国人群DGI-Ⅱ的突变热点.%Objective: To collect families with hereditary dentin disorders in Chinese population and perform analysis on phenotype and disease classification, as well as to screen the mutations on the candidate gene DSPP, and to explore the correlation between gene mutation and phenotype.Methods: Comprehensive oral examination was performed for available affected individuals in collected families with dentinogenesis imperfacta (DGI).Clinical phenotypes and classification diagnosis were analyzed in each family.Genomic DNA was extracted from peripheral blood in all investigated members.Mutations screening was performed by amplifying all coding regions and splicing junctions of DSPP and sequencing the products.The results were analyzed by BLAST searching, combined with GENBANK polymorphisms and mutations database of DSPP.Results: A total of 3 families with DGI were enrolled in the study.One of them presents unique xerostomia phenotype besides the typical clinical features of DGI type Ⅱ (DGI-Ⅱ).Among 3 families, no mutation was found in the DSP region, and a common frameshift mutation c.3546-3550delTAGCAinsG of DSPP was revealed in DPP coding region in two families, which was identical to a previous reported mutation in other family with DGI-Ⅱ.Conclusions: The present study reported a novel phenotype in DGI-Ⅱ, and further suggested that DPP mutations might be an important pathogenic factor for DGI-Ⅱ, and that c.3546-3550delTAGCAinsG might be a hot point mutation of DSPP in Chinese population.
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