Large deletions in the polycystic kidney disease 1 (PKD1) gene.
Large deletions in the polycystic kidney disease 1 (PKD1) gene.
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DOI：
10.1002/humu.9208
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发表时间：
2004-01-01
期刊：
影响因子：
3.9
通讯作者：
Peters, Dorien J M
中科院分区：
文献类型：
--
作者：
Ariyurek, Yavuz;Lantinga-van Leeuwen, Irma;Peters, Dorien J M
自从识别出常染色体显性遗传性多囊肾病患者PKD 1和PKD 2突变的基因以来，通过传统的基于PCR的突变检测方法发现了这两个基因中大量不同的种系突变。然而，在大约40%的PKD 1家族中，致病突变仍有待阐明。复杂的生殖细胞系重排通常无法通过这些标准诊断技术检测到。为了检测PKD1基因中的大缺失，我们进行了场反转凝胶电泳（FIGE），然后用在该基因的独特区域和重复区域中选择的探针进行Southern印迹分析。我们的分析显示125例患者中有4例缺失，表明PKD1的大缺失是罕见的。可能的是，具有也影响邻近的多发性硬化症复合体2（TSC 2）基因的缺失的患者将被诊断为结节性硬化症患者。推测位于第21内含子的特异性多聚嘧啶序列和位于第22内含子的小片段可能在ADPKD的发病中起作用。由于这一区域是非常困难的PCR扩增，我们分析了5.8 kb的BamHI片段，含有多嘧啶道。我们没有观察到与疾病相关的改变，尽管我们在PKD 1或其同源物中检测到两种不同的罕见变异。
Since identification of the genes mutated in patients with Autosomal Dominant Polycystic Kidney Disease, PKD1 and PKD2, a large number of different germ line mutations in both genes have been found by conventional PCR-based mutation detection methods. Nevertheless, in approximately 40% of the PKD1 families the disease-causing mutation remains to be elucidated. Complex germ line rearrangements are often not detectable by these standard diagnostic techniques. To detect large deletions in the PKD1 gene we performed Field Inversion Gel Electrophoresis (FIGE) followed by Southern blot analysis with probes selected in the unique and in the reiterated region of this gene. Our analysis revealed 4 deletions in 125 patients, indicating that large deletions in PKD1 are rare. Likely, patients with a deletion that also affects the neighbouring Tuberous Sclerosis Complex 2 (TSC2) gene will be diagnosed as patients with tuberous sclerosis. It was speculated that the exceptional polypyrimidine tract located in intron 21 and the small tract in intron 22, might play a role in the pathogenesis of ADPKD. Since this region is extremely difficult to amplify by PCR, we analysed the 5.8 kb BamHI fragment that contains the polypyrimidine tracts. We did not observe a disease-linked alteration although we detected two different rare variants either in PKD1 or in one of its homologues.