摘要
目的探讨编码基因COL4A5mRNA的表达与X连锁Alport综合征(xLAS)女性临床表型之间的关系。方法以已确诊其COL4A5为缺失突变的女性为研究对象,以其皮肤成纤维细胞中α5(Ⅳ)链的突变mRNA表达量占总mRNA表达量(即突变mRNA表达量与正常mRNA表达量之和)的50％为界分组,并结合临床资料分析。结果各患者均有持续性镜下血尿,突变mRNA表达多于正常mRNA表达的患者还常有肉眼血尿,而且伴有程度较重的蛋白尿;而突变mRNA表达少于或等于正常mRNA表达的患者常无肉眼血尿,而且不伴有蛋白尿或者蛋白尿的程度轻微。各患者的蛋白尿程度与其α5(Ⅳ)链的突变mRNA与总mRNA之比呈直线相关,有显著统计学意义。结论突变COL4A5基因mRNA表达量的差异可能是影响XLAS女性临床表型的因素之一,突变等位基因mRNA的表达量居多的XLAS女性临床症状相对重。
Objective To understand the different phenotype based on COL4A5 mutations and to analyze the correlation between mutant mRNA expression of COL4A5 gene and phenotype variability of XLAS females. Methods Skin biopsy specimens were obtained from 6 XLAS females with confirmed COL4A5 deletion mutations. Total RNA was isolated from cultured skin fibroblasts and RT-PCR was performed to amplify the fragment including the mutation sequences of COL4A5 gene. The PCR products were electrophoresed with 8% polyacrylamide gel. Each fragment of PCR product revealed under polyacrylamide gel was further analyzed with the optical absorptance (A). The A ratio of mutant over total mRNA of COL4A5 gene (total mRNA means the mutant mRNA plus normal mRNA) was analyzed with different phenotypes. Results Besides microscopic hematuria, the females often had gross hematuria and persistent and severe proteinuria when the mutant a5 (IV) mRNA expression was more than the normal. Whereas the XLAS females didn't had gross hematuria and proteinuria or had discontinuous and mild proteinuria when the mutant α5 (Ⅳ) mRNA expression was less than the normal. The proteinuria was positively correlated with the expression ratio of mutant over total mRNA of COL4A5 gene in the females. Conclusions The quantity of the mutant mRNA expression of COL4AS gene is correlated with the phenotypic severity of XLAS females. The XLAS females with much more mutant mRNA expression of COL4A5 gene show more severe phenotypes of AS.
出处
《中华肾脏病杂志》
CAS
CSCD
北大核心
2005年第1期13-17,共5页
Chinese Journal of Nephrology
基金
国家自然科学基金(39770780
39970775
30371495)
关键词
遗传性肾炎
表型
遗传异质性
信使RNA
Nephritis, hereditary
Phenotype
Genetic heterogeneity
Messenger RNA
