West China College of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
Gene. 2012 Dec 15;511(2):420-6. doi: 10.1016/j.gene.2012.09.042. Epub 2012 Sep 25.
Amelogenesis imperfecta, dentinogenesis imperfecta, and dentin dysplasia are the most common non-syndromic dental disorders. In this study, we analysed and localised the gene(s) responsible for inherited non-syndromic dental disorders in a Chinese family.
This study identified and researched non-syndromic dental disorders in a four-generation Chinese family, including four affected individuals whose clinical phenotype was atypical. Linkage analysis with seven polymorphic markers that localise to six different autochromosomes showed that the family was linked through chromosome 4q. All exons and exon-intron boundaries of dentin sialophosphoprotein (DSPP), enamelin (ENAM), and ameloblastin (AMBN), which are located on chromosome 4q, were sequenced in nine of the family members.
Direct DNA sequence analysis revealed the existence of a G to A transversion in exon 4 (g.13081786G>A, c.727G>A, p.Asp243Asn, based on reference sequences NM_014208.3) of the DSPP gene, and this sequence variation correlated exactly with the presence of the disease.
These results indicate that mutation p.Asp243Asn is a highly probable cause of non-syndromic dental disorder in this Chinese family. The presence of symptom heterogeneity is possible, as the clinical classification system is hampered by the lack of close correlation between the subtype and the molecular defect.
釉质不全，牙本质不全和牙本质发育不良是非综合征性牙科疾病中最常见的三种类型。在本研究中，我们分析并定位了一个中国家庭中遗传非综合征性牙科疾病的相关基因。
本研究鉴定并研究了一个四代中国家庭中的非综合征性牙齿疾病，其中包括 4 名临床表现不典型的受影响个体。使用定位在 6 条不同常染色体上的 7 个多态性标记的连锁分析显示，该家庭与染色体 4q 连锁。在 9 名家庭成员中对位于 4q 染色体上的牙本质涎磷蛋白（DSPP）、釉原蛋白（ENAM）和釉基质蛋白（AMBN）的所有外显子和外显子-内含子边界进行了测序。
直接 DNA 序列分析显示，DSPP 基因第 4 外显子（g.13081786G>A，c.727G>A，p.Asp243Asn，基于参考序列 NM_014208.3）中存在 G 到 A 的颠换，该序列变异与疾病的存在完全相关。
这些结果表明，突变 p.Asp243Asn 很可能是该中国家庭中非综合征性牙齿疾病的原因。由于临床分类系统缺乏亚型与分子缺陷之间的紧密相关性，因此症状异质性的存在是可能的。
