Stekrová Jitka, Reiterová Jana, Merta Miroslav, Damborsky Jirt, Zidovská Jana, Kebrdlová Vera, Kohoutová Milada
Department of Biology and Medical Genetics, Charles University, Prague, Czech Republic.
Nephrol Dial Transplant. 2004 May;19(5):1116-22. doi: 10.1093/ndt/gfh083. Epub 2004 Feb 19.
Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous and caused by mutations in at least three different loci. Based on linkage analysis, mutations in the PKD2 gene are responsible for approximately 15% of the cases. PKD2-linked ADPKD is supposed to be a milder form of the disease, its mean age of end-stage renal failure (ESRF) approximately 20 years later than PKD1.
We screened all coding sequences of the PKD2 gene in 115 Czech patients. From dialysis centres in the Czech Republic and from the Department of Nephrology of the General Hospital in Prague, we selected 52 patients (29 males, 23 females), who reached ESRF after the age of 63, and 10 patients (three males, seven females) who were not on renal replacement therapy at that age. The age of 63 was used as the cut-off because it is between the recently published ages of onset of ESRF for PKD1 and PKD2. From PKD families we also selected 53 patients (26 males, 27 females) who could be linked to either the PKD1 or PKD2 genes by linkage analysis. An affected member from each family was analysed by heteroduplex analysis (HA) for all 15 coding regions. Samples exhibiting shifted bands on gels were sequenced.
We detected 22 mutations (six new mutations)-14 mutations in 62 patients (23%) with mild clinical manifestations, eight in 53 families (15%) with possible linkage to both PKD genes. As the detection rate of HA is approximately 70-80%, we estimate the prevalence of PKD2 cases in the Czech ADPKD population to be 18-20%. We identified nonsense mutations in eight patients (36.5%), frameshifting mutations in 12 patients (54.5%) and missense mutations in two patients (9%).
In this study in the Czech population we identified 22 mutations (six of which were new mutations). The prevalence of PKD2 cases was 18-20% and the mean age of ESRF was 68.3 years. An at-least weak hot spot in exon 1 of the PKD2 gene was found.
常染色体显性多囊肾病（ADPKD）具有遗传异质性，由至少三个不同基因座的突变引起。基于连锁分析，PKD2基因突变约占病例的15%。PKD2相关的ADPKD被认为是该病的一种较轻形式，其终末期肾衰竭（ESRF）的平均年龄比PKD1相关的ADPKD约晚20年。
我们对115名捷克患者的PKD2基因所有编码序列进行了筛查。从捷克共和国的透析中心和布拉格综合医院肾病科，我们选取了52名患者（29名男性，23名女性），他们在63岁以后进入ESRF，以及10名患者（3名男性，7名女性），他们在该年龄未接受肾脏替代治疗。选择63岁作为分界点，因为它介于最近公布的PKD1和PKD2的ESRF发病年龄之间。我们还从PKD家族中选取了53名患者（26名男性，27名女性），他们可通过连锁分析与PKD1或PKD2基因连锁。对每个家族的一名患病成员的所有15个编码区域进行异源双链分析（HA）。对凝胶上出现条带迁移的样本进行测序。
我们检测到22个突变（6个新突变）——62名临床表现较轻的患者中有14个突变（23%），53个可能与两个PKD基因连锁的家族中有8个突变（15%）。由于HA的检测率约为70 - 80%，我们估计捷克ADPKD人群中PKD2病例的患病率为18 - 20%。我们在8名患者（36.5%）中鉴定出无义突变，12名患者（54.5%）中鉴定出移码突变，2名患者（9%）中鉴定出错义突变。
在这项针对捷克人群的研究中，我们鉴定出22个突变（其中6个是新突变）。PKD2病例的患病率为18 - 20%，ESRF的平均年龄为68.3岁。在PKD2基因的外显子1中发现了一个至少较弱的热点区域。
