Ⅱ型乳光牙家系细胞外基质磷酸化糖蛋白、骨涎蛋白基因的检测

Mutation analysis of MEPE and IBSP genes in two DGI-Ⅱfamilies

目的通过对2个遗传性牙本质发育不全Ⅱ型家系的细胞外基质磷酸化糖蛋白(matrixextracellularphosphoglycoprotein,MEPE)、骨涎蛋白(BonesialoproteinⅡ,IBSP)进行突变检测,寻找Ⅱ型乳光牙致病基因,为临床诊断、基因治疗提供分子基础。方法在MEPE、IBSP基因内设计引物,经PCR和DNA测序对基因编码序列及其临近内含子进行突变检测。结果在MEPE基因发现c.1027G>A的碱基变化,该变化导致MEPE出现V330I的氨基酸变化,在IBSP发现c.797G>A的碱基变化,该变化导致IBSP出现G219R的氨基酸变化。两种变化在家系内与表型不存在一一对应关系。结论排除了MEPE、IBSP为两个DGI-Ⅱ型家系致病基因的可能,进一步缩小了候选基因范围,为最终的基因治疗提供基础。

Aim To detect the mutation of matrix extracellular phosphoglycoprotein (MEPE) and bone sialoprotein Ⅱ(IBSP) in two Chinese DGI Ⅱfamilies for the pathogenic genes as the basis of clinical diagnosis and gene therapy.Methods PCR and DNA sequencing were subjected to detect the possible mutations in MEPE and IBSP coding sequence and splice junction intron sequences.Results A c.1027G >A base pair transversion with a predicted amino acid residue change V330I were detected in MEPE; a c.797G >A base pair transversion with a predicted amino acid residue change G219R were detected in IBSP, without the correlation between the families and phenotypes.Conclusion MEPE and IBSP were excluded as the pathogenic gene of DGI Ⅱin the two families, further reducing the candidate genes for the future gene therapy and diagnosis.