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目的探讨X连锁显性遗传Alport综合征(XLAS)女性患者临床表型的差异与不同组织X染色体失活方式的关系。方法以确诊的36例XLAS女性患者为研究对象,以尿蛋白作为判断临床表型严重程度的指标,检测所有患者外周血和其中12例患者皮肤组织的X染色体失活方式。采用限制性内切酶HpaⅡ酶消化后PCR扩增雄性激素受体基因第1外显子CAG重复序列多态性的方法检测X染色体失活。结果随着尿蛋白水平的增加,XLAS女性患者外周血中COL4A5致病等位基因所在X染色体失活比例的平均值降低,二者呈负相关(r=-0.543,P=0.002);XLAS女性患者尿蛋白水平与皮肤成纤维细胞中COL4A5致病等位基因所在X染色体失活比例无相关性(r=-0.131,P=0.701)。结论X染色体的失活方式也许能解释XLAS女性患者的临床表型差异,通过分析外周血中X染色体失活方式也许能够早期预测XLAS女性患者的预后。
Objective To investigate the relationship between clinical phenotypes and X chromosome inactivation in different X-linked dominant Alport syndrome (XLAS) female patients. Methods Twenty-six female patients with XLAS were enrolled in this study. Urine protein was used as an index to determine the severity of clinical phenotype. X-deactivation patterns of peripheral blood and all skin tissues of 12 patients were detected. X-chromosome inactivation was detected by PCR amplification of the CAG repeat exon 1 of the androgen receptor gene after restriction endonuclease HpaII digestion. Results With the increase of urinary protein level, the average proportion of X chromosome inactivation alleles of COL4A5 in peripheral blood of XLAS female patients decreased, the two were negatively correlated (r = -0.543, P = 0.002) There was no correlation between urinary protein levels and X chromosome inactivation ratio of COL4A5-producing alleles in skin fibroblasts (r = -0.131, P = 0.701). Conclusion X-chromosome inactivation patterns may explain the clinical phenotypic differences in XLAS women and the prognosis of XLAS female patients may be predicted early by analyzing the X chromosome inactivation pattern in peripheral blood.