【摘要】 目的研究Alport综合征(AS)致病基因COL4A5突变情况。方法收集并抽提2005年上海地区AS患者及其所有家庭成员29例的基因组DNA,并根据致病基因设计相关引物,分别检测患者和100个正常人血液DNA以及患者皮肤的cDNA碱基序列。结果发现AS基因组DNA的COL4A5基因c.609+5G>A高度保守区存在5G>A突变,而100个正常人均无该突变,该位点尚未见文献报道;同时发现患者COL4A5基因mRNA不能正常翻译。而COL4A5基因已报道的位点,并未在本家系中发现。结论 AS患者c.609+5G高度保守存在5G>A突变,证实该变异可能使COL4A5基因剪接发生错误而导致基因mRNA不能正常翻译。更多还原

【Abstract】 Objective To determine mutation of COL4A5,the pathogenic gene,via performing pedigree analysis on Alport’s syndrome in Shanghai. Methods The genomic DNA was extracted from 29 subjects in a pedigree.Corresponding primers were synthesized for cDNA sequencing of blood and cutaneous tissue in 29 subjects and 100 normal controls. Results The 5G>A mutation at highly conserved region of c.609+5G>A in COL4A5 gene,although lack of literature documentation,was detected in patients with Alport’s syndrome,but not in 100 normal controls.Also revealed was the inability of COL4A5 mRNA to translate in a normal manner.By contrast,the documented regions of COL4A5 gene were absent in these pedigree members. Conclusion The 5G>A mutation in c.609+5Gm,the highly conserved region,is found to be associated with splicing errors of COL4A5 gene,which in turn leads to inability of normal translation of mRNA.更多还原