Roelfsema J H, Spruit L, Saris J J, Chang P, Pirson Y, van Ommen G J, Peters D J, Breuning M H
Department of Human Genetics, Sylvius Laboratory, Leiden University, Leiden, The Netherlands.
Am J Hum Genet. 1997 Nov;61(5):1044-52. doi: 10.1086/301600.
The principle cause of one of the most prevalent genetic disorders, autosomal dominant polycystic kidney disease, involves mutations in the PKD1 gene. However, since its identification in 1994, only 27 mutations have been published. Detection of mutations has been complicated because the greater part of the gene lies within a genomic region that is reiterated several times at another locus on chromosome 16. Amplification of DNA fragments in the repeated part of the PKD1 gene will lead to coamplification of highly homologous fragments derived from this other locus. These additional fragments severely hamper point-mutation detection. None of the point mutations published to date are located in the repeated part of the PKD1 gene. However, we have reduced the problems posed by the strong homology, by using the protein-truncation test, and we have identified eight novel mutations, seven of which are located in the repeated part of the PKD1 gene.
最常见的遗传性疾病之一——常染色体显性多囊肾病的主要病因涉及PKD1基因突变。然而，自1994年该基因被识别以来，仅有27种突变被公布。由于该基因的大部分位于基因组区域内，而此区域在16号染色体的另一位点上重复出现了数次，因此突变检测变得复杂。PKD1基因重复部分的DNA片段扩增会导致来自其他位点的高度同源片段共同扩增。这些额外的片段严重妨碍了点突变检测。迄今公布的点突变均不在PKD1基因的重复部分。不过，我们通过使用蛋白质截短试验减少了强同源性带来的问题，并且识别出了8种新突变，其中7种位于PKD1基因的重复部分。
