Dental structural diseases mapping to human chromosome 4q21
Dental structural diseases mapping to human chromosome 4q21
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DOI：
10.1080/03008200390181780
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发表时间：
2003-01-01
影响因子：
2.9
通讯作者：
MacDougall, M
中科院分区：
文献类型：
--
作者：
MacDougall, M
影响牙齿结构的遗传性疾病已根据影响牙釉质与牙本质的组织及其遗传模式常染色体显性、常染色体隐性或X连锁进行分类。分子遗传学和人类基因组计划的进展为鉴定参与人类疾病发病机制的基因提供了实质性进展。这些包括影响釉质和牙本质形成的牙科疾病：牙釉质形成障碍（AI）、牙本质形成障碍（DGI）II型和III型以及牙本质发育不良（DD）II型。使用大型信息家族的连锁研究提供了深入了解，确定了人类染色体4 q21上的两个近端基因簇，其中包含五种牙齿结构性疾病的关键基因座。与常染色体显性遗传型AI相关的研究（约占所有病例的85%）已经确定了两种类型AI与4 q21的连锁关系：局部发育不良型和平滑型发育不良型AI。两种釉基质蛋白质，成釉蛋白和釉蛋白，已被映射在这些疾病的关键区域。位于更接近端粒的是包含三种牙本质疾病的基因座的另一簇：DGI II型、III型和DD II型。位于这些疾病的重叠部分内的是牙本质/骨基因簇，其包含骨桥蛋白、骨唾液蛋白、基质细胞外磷酸糖蛋白（也称为成骨细胞/骨细胞因子45或骨调节蛋白）、牙本质基质蛋白1和牙本质唾液磷酸蛋白。持续的分子遗传学研究将有助于在这两个牙齿基质基因簇中识别新的牙齿基质蛋白，以及识别额外的常染色体显性AI基因座。
Genetic diseases affecting tooth structure have been classified by the tissue affected enamel versus dentin, and their pattern of inheritance autosomal dominant, autosomal recessive, or X-linked. Advances in molecular genetics and the Human Genome Project have provided substantial progress regarding the identification of genes involved in the pathogenesis of human diseases. These include dental diseases affecting enamel and dentin formation: amelogenesis imperfecta (AI), dentinogenesis imperfecta (DGI) types II and III, and dentin dysplasia (DD) type II. Linkage studies using large informative families have provided insight identifying two proximal gene clusters on human chromosome 4q21 that contain the critical loci for five dental structural diseases. Studies related to the autosomal dominant forms of AI, representing similar to85% of all cases, have established linkage to 4q21 for two forms: local hypoplastic and smooth hypoplastic AI. Two enamel matrix proteins, ameloblastin and enamelin, have been mapped within the critical regions for these diseases. Located more toward the telomere is another cluster containing loci for three dentin diseases: DGI type II, type III, and DD type II. Located within an overlapping segment of these diseases is a dentin/bone gene cluster that contains osteopontin, bone sialoprotein, matrix extracellular phosphoglycoprotein also known as osteoblast/osteocyte factor 45 or osteoregulin, dentin matrix protein 1, and dentin sialophosphoprotein. Continuing molecular genetic studies will facilitate the identification of novel tooth matrix proteins within these two tooth matrix gene clusters as well as the identification of additional autosomal dominant AI loci.