X连锁显性遗传Alport综合征女性患者临床表型与不同组织X染色体失活方式的关系  

Correlation between X-Inactivation of Different Tissues and Phenotypes in Female with X-Linked Alport Syndrome

作　　者：张宏文[1] 丁洁[1] 王芳[1] 

机构地区：[1]北京大学第一医院儿科,北京100034

出　　处：《实用儿科临床杂志》2010年第5期320-323,共4页Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金(30801252)

摘　　要：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 explore the correlation between phenotypes in female with X - linked Alport syndrome （XLAS） and X - inactivation of different tissues. Methods Thirty - six female diagnosed as XLAS were studied, and proteinuria was taken as a marker of the severity of clinical phenotypes. X - inactivation patterns were analyzed in peripheral blood cells of 36 XLAS female and in skin fibroblasts of 12 XLAS female. The X - inactivation analysis was performed by using Hpa 11 predigestion of DNA followed by polymerase chain reaction （PCR） of the highly polymorphic CAG repeat of the androgen receptor gene. Results The average X - inactivation levels of the mutant allele decreased while the degree of proteinuria increased, so there was a negative correlation between the degree of proteinuria and the X- inactivation ratios of the mutant allele in blood cells （r = -0. 543,P = 0. 002 ）. However, there was no correlation between the degree of proteinuria and the X - inactivation ratios of the mutant allele in skin fibroblasts（ r = -0. 131 ,P = 0. 701 ）. Conclusions X - inactivation ratios might explain partially the diverse phenotypes in XLAS female patients, which suggested that the prognosis of XLAS female might be predicted via analysis of the X - inactivation in peripheral blood cells.

关 键 词：X连锁显性遗传 女性患者 临床表型 X染色体失活 

分 类 号：R692[医药卫生—泌尿科学]