Zhang Shuzhong, Mei Changlin, Zhang Dianyong, Dai Bing, Tang Bing, Sun Tianmei, Zhao Haidan, Zhou Yukun, Li Lin, Wu Yumei, Wang Wenjing, Shen Xuefei, Song Ji
Division of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
Nephron Exp Nephrol. 2005;100(2):e63-76. doi: 10.1159/000084572. Epub 2005 Mar 17.
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in two genes, PKD1 and PKD2. The complexity of these genes, particularly PKD1, has complicated genetic screening, though recent advances have provided new opportunities for amplifying these genes. In the Han Chinese population, no complete mutational analysis has previously been conducted across the entire span of PKD1 and PKD2. Here, we used single-strand conformation polymorphism (SSCP) analysis to screen the entire coding sequence of PKD1 and PKD2 in 85 healthy controls and 72 Han Chinese from 24 ADPKD pedigrees. In addition to 11 normal variants, we identified 17 mutations (12 in PKD1 and 5 in PKD2), 15 of which were novel ones (11 for PKD1 and 4 for PKD2). We did not identify any seeming mutational hot spots in PKD1 and PKD2. Notably, we found several disease-associated C-T or G-A mutations that led to charge or hydrophobicity changes in the corresponding amino acids. This suggests that the mutations cause conformational alterations in the PKD1 and PKD2 protein products that may impact the normal protein functions. Our study is the first report of screenable mutations in the full-length PKD1 and PKD2 genes of the Han Chinese, and also offers a benchmark for comparisons between Caucasian and Han ADPKD pedigrees and patients.
常染色体显性多囊肾病（ADPKD）由两个基因PKD1和PKD2的突变引起。这些基因的复杂性，尤其是PKD1，使得基因筛查变得复杂，不过最近的进展为扩增这些基因提供了新机会。在汉族人群中，此前尚未对PKD1和PKD2的整个区域进行完整的突变分析。在此，我们使用单链构象多态性（SSCP）分析对85名健康对照者以及来自24个ADPKD家系的72名汉族个体的PKD1和PKD2的整个编码序列进行筛查。除了11个正常变异外，我们鉴定出17个突变（PKD1中有12个，PKD2中有5个），其中15个是新突变（PKD1中有11个，PKD2中有4个）。我们在PKD1和PKD2中未发现任何明显的突变热点。值得注意的是，我们发现了几个与疾病相关的C-T或G-A突变，这些突变导致相应氨基酸的电荷或疏水性发生变化。这表明这些突变会导致PKD1和PKD2蛋白产物的构象改变，可能影响正常的蛋白功能。我们的研究是关于汉族人群PKD1和PKD2全长基因可筛查突变的首次报告，也为白种人和汉族ADPKD家系及患者之间的比较提供了一个基准。
