Center for Human Genetics and Laboratory Medicine Dr Klein and Dr Rost, Martinsried, Germany.
Nephrol Dial Transplant. 2011 Jul;26(7):2181-8. doi: 10.1093/ndt/gfq720. Epub 2010 Nov 29.
Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic renal disorder with an incidence of 1:1000. Mutations in two genes (PKD1 and PKD2) have been identified as causative. Eighty-five percent of patients with ADPKD carry their mutation in the PKD1 gene. So far, > 500 mutations for PKD1 and > 120 mutations for PKD2, respectively, are known.
In this study, we performed mutation analysis of PKD1 and PKD2 by exon sequencing in patients during routine molecular diagnostics for ADPKD.
In total, 60 mutations were identified in 93 patients representing a mutation detection efficiency of 64.5%. Fifty-two mutations were identified in PKD1 (86.7%) and 8 in PKD2 (13.3%). These include 41 novel mutations detected in PKD1 and 5 novel mutations in PKD2. Accordingly, our data expand the spectrum of known PKD mutations by 8% for PKD1 (41/513) and 4.2% for PKD2 (5/120). These results are in agreement with the detection ranges of 42%, 63% and 64% for definitive disease-causing mutations, and 78%, 86% and 89% for all identified variants reported in several comprehensive mutation screening reports.
The increased number of known mutations will facilitate future studies into genotype-phenotype correlations.
常染色体显性多囊肾病（ADPKD）是一种常见的遗传性肾脏疾病，发病率为 1:1000。已经确定两个基因（PKD1 和 PKD2）的突变是致病原因。85%的 ADPKD 患者在 PKD1 基因中携带其突变。到目前为止，PKD1 有 >500 种突变，PKD2 有 >120 种突变。
在这项研究中，我们在常规的 ADPKD 分子诊断中对 PKD1 和 PKD2 进行外显子测序，以分析患者的突变情况。
在 93 名患者中总共发现了 60 个突变，突变检测效率为 64.5%。在 PKD1 中发现了 52 个突变（86.7%），在 PKD2 中发现了 8 个突变（13.3%）。其中包括在 PKD1 中检测到的 41 个新突变和在 PKD2 中检测到的 5 个新突变。因此，我们的数据使 PKD1 的已知突变谱扩展了 8%（41/513），PKD2 的扩展了 4.2%（5/120）。这些结果与几个全面突变筛查报告中报道的明确致病突变的检测范围 42%、63%和 64%，以及所有鉴定变异的检测范围 78%、86%和 89%一致。
已知突变数量的增加将有助于未来进行基因型-表型相关性研究。
