遗传性牙本质发育不全Ⅱ型家系致病基因的连锁分析及DMP1的突变检测

摘要

目的：对中国江苏淮阴一个遗传性牙本质发育不全Ⅱ型家系的致病基因进行定位，同时对该疾病的候选基因之一DMP1进行突变检测。方法：用位于4q21区域的7个微卫星位点对家系进行遗传连锁分析，并通过聚合酶链反应-单链构象多态分析（PCR－SSCP）和DNA测序方法对DMP1基因进行突变检测。结果：所选的7个位点中，除D4S451和D4S1534之外，最大Lod值Zmax均大于3(θ＝0)；PCR－SSCP和测序结果显示DMP1 Exon 2～6均无突变。结论：遗传性牙本质发育不全Ⅱ型与位于4q21区域的微卫星位点GATA62A11、DSP、DMP1、SPP1和D4S1563连锁；排除了DMP1做为该疾病致病基因的可能性。%AIM：To study the location of pathogenic gene in dentinogenesis imperfecta type Ⅱ,and to screen the mutation of DMP1 gene. METHODS: The families were analyzed with linkage studies using 7 highly polymorphic microsatellite DNA markers in the region of 4q21. PCR-SSCP and DNA sequencing were employed to detect the mutation of DMP1. RESULT: The maximum Lod scroes of the 7 markers were: D4S451,Zmax=2.76(θ＝0.1); D4S1534,Zmax=1.65(θ＝0); GATA62A11,Zmax=7.63(θ＝0); DSP,Zmax=6.06(θ＝0); DMP1,Zmax=8.24(θ＝0); SPP1,Zmax=8.39(θ＝0); D4S1563,Zmax=7.34(θ＝0) respectively. No mutation was detected in DMP1. CONCLUSION: The pathogenic gene of dentinogenesis imperfecta type Ⅱ is linked to GATA62A11,DSP,DMP1,SPP1 and D4S1563 in 4q21; excluding the DMP1 gene from a causative role in the pathogenesis of DGI-Ⅱ.