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

Pathogenic gene linkage analysis and DMP1 gene mutation assay in dentinogenesis imperfecta type Ⅱ

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 4q2 1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D4S45 1和D4S15 34之外 ,最大Lod值Zmax均大于 3(θ =0 ) ;PCR -SSCP和测序结果显示DMP1Exon 2～ 6均无突变。结论 :遗传性牙本质发育不全Ⅱ型与位于 4q2 1区域的微卫星位点GATA6 2A11、DSP、DMP1、SPP1和D4S15 6 3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,Z max =2.76(θ=0.1); D4S1534,Z max =1.65(θ=0); GATA62A11,Z max =7.63(θ=0); DSP,Z max =6.06(θ=0); DMP1,Z max =8.24(θ=0); SPP1,Z max =8.39(θ=0); D4S1563,Z max =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. [