遗传性釉质发育不全家系致病基因的定位研究

目的定位遗传性釉质发育不全（AI）家系的致病基因。方法收集1个常染色体显性AI家系，提取该家系19名成员（其中患者9例）的外周血DNA，选择横跨釉蛋白基因、成釉蛋白基因、釉丛蛋白基因、基质金属蛋白酶基因、丝氨酸蛋白酶基因5个候选基因的短串联重复序列（STR），进行PCR扩增，经变性聚丙烯酰胺凝胶电泳确定基因型，并进行连锁分析。结果得到19名个体的8个STR位点的基因型，分别为D1s498、D1s2343、D4s1543、D4s2361、D4s2969、D11s1339、mmp20、D19s246。连锁分析结果显示各位点的LOD值在重组率为0时均小于1，不支持该家系的致病基因与5个侯选基因上的STR位点的连锁关系。结论连锁分析结果不支持该家系致病基因定位于已知基因座处，提示至少某些常染色体显性AI家系的致病基因不是文献所报道的AI候选基因，进一步证实了常染色体显性遗传性釉质发育不全的遗传异质性。

Exclusion of Candidate Genes in a Family with Amelogenesis Imperfecta

Objective To localize the gene(s) responsible for autosomal dominant hypocalcified amelogenesis imperfecta in a Chinese family. Methods A Chinese family which was diagnosed as autosomal dominant hypocalcified amelogenesis imperfecta(AI) was studied. Venous blood from nineteen family members was collected and genomic DNA was extracted from the blood. Eight short tandem repeats(STRs) spanning five hereditary AI candidate genes were selected and linkage analysis between the genetic markers and the disease loci was performed. Results Genotype of the eight STRs were acquired, the linkage analysis result can not support that the gene for AI pedigrees was linked to ENAM, AMBN, TUF1, KLK4 or MMP-20. Conclusion The results can not support all proposed candidate gene regions as causal for autosomal dominant hypocalcified AI in this family. These linkage findings provide further evidence for genetic heterogeneity among families with autosomal dominant AI and indicate that, at least, some forms of autosomal dominant AI are not caused by a gene in the five most commonly reported AI candidate genes.