一个遗传性牙本质发育不全家系的分子遗传研究

Mutation analysis of a Chinese family with genetic dentinogenesis imperfecta

目的研究一个常染色体显性牙本质发育不全家系发病的遗传基础。方法通过对一个DSPP家系临床检查和家族史调查，连锁分析和DSPP基因的突变检测，以及限制性片段长度多态分析方法，分析该家系发病的分子基础。结果连锁分析发现，该疾病致病基因与微卫星标记D4S1534完全连锁，对位于该区域的DSPP基因进行测序分析，发现一个新的致病突变（C．49C→T，p．Prol7Ser），该突变位于DSPP基因的第1外显子。该家系所有患者中都检测到了这一致病突变，但家系中的正常个体和100个无亲缘关系的正常人中未发现这个突变。结论p．Pr017Ser是牙本质发育不全Ⅱ型致病基因DSPP的一个新的致病突变。我们的研究进一步拓展了对牙本质发育不全疾病分子遗传基础的认识。

Objective To study the genetic etiology of an autosomal dominant dentinogenesis imperfecta in a Chinese family. Methods The molecular change of the disease in the family was analyzed through the clinical examination, linkage analysis, mutational screening of the DSPP gene and restriction fragment length polymorphism analysis. Results The disease related gene was completely linked with microsatellite marker D4S1534. We found a novel mutation in the first exon of the DSPP gene （c. 49C→T, p. ProlTSer）. All patients in the family had the mutation, while this mutation was not observed in the normal individuals of this family and 100 unrelated controls. Conclusion The p. Prol7Ser identified in the family was a new pathogenic mutation. Our finding provided further understanding of the molecular mechanism of dentinogenesis Imperfecta.