Lench N J, Winter G B
Division of Oral Surgery, Leeds Dental Institute, United Kingdom.
Hum Mutat. 1995;5(3):251-9. doi: 10.1002/humu.1380050310.
Amelogenins are an heterogenous family of proteins produced by ameloblasts of the enamel organ during tooth development. Disturbances of enamel formation occur in amelogenesis imperfecta, a clinically heterogenous group of inherited disorders characterised by defective enamel biomineralisation. An amelogenin gene, AMGX, has been mapped to the short of the X chromosome (Xp22.1-p22.3) and has been implicated in the molecular pathology of X-linked amelogenesis imperfecta (AIH1). We have identified three families exhibiting AIH1 and screened the AMGX gene for mutations using single-strand conformational polymorphism analysis and DNA sequencing. Three novel mutations were identified: a C-T substitution in exon 5, and a G-T substitution and single cytosine deletion in exon 6, confirming the existence of extensive allelic heterogeneity in this condition. The identification of family-specific mutations will enable early identification of affected individuals and correlation of clinical phenotype with genotype will facilitate an objective system of disease classification.
釉原蛋白是牙齿发育过程中由釉质器官的成釉细胞产生的一类异质性蛋白质。釉质形成障碍发生在成釉不全中，这是一组临床异质性的遗传性疾病，其特征是釉质生物矿化缺陷。一个釉原蛋白基因AMGX已被定位到X染色体短臂（Xp22.1-p22.3），并与X连锁成釉不全（AIH1） 的分子病理学有关。我们鉴定了三个表现出AIH1的家系，并使用单链构象多态性分析和DNA测序对AMGX基因进行突变筛查。鉴定出三个新的突变：外显子5中的C-T替换，以及外显子6中的G-T替换和单个胞嘧啶缺失，证实了这种情况下存在广泛的等位基因异质性。家族特异性突变的鉴定将有助于早期识别受影响的个体，临床表型与基因型的相关性将有助于建立一个客观的疾病分类系统。
