Evidence of a third ADPKD locus is not supported by re-analysis of designated PKD3 families.
Evidence of a third ADPKD locus is not supported by re-analysis of designated PKD3 families.
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DOI：
10.1038/ki.2013.227
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发表时间：
2014-02
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
--
作者：
PKD 1和PKD 2的突变与常染色体显性多囊肾病（ADPKD）相关。在5个已发表的欧洲或北美ADPKD家族中，没有明显的PKD 1/PKD 2连锁，这表明存在第三个位点，即PKD 3。在这里，我们通过更新临床信息、尽可能重新采样和PKD 1/PKD 2突变筛查来重新评估这些家族。在法裔加拿大家庭中，我们确定PKD 1：p.D3782_V3783insD，两个人的误诊和样本污染解释了缺乏联系。在葡萄牙的家庭，PKD 1：p.G3818A分离的疾病在10个人在三代可能误诊的一个人，样品污染，并使用遥远的微卫星标记解释的连锁差异。突变PKD 2：c.213delC在保加利亚家族中被发现，其中两个个体的假阳性诊断导致连锁失败。一个受影响的儿子，但不是母亲，在意大利家庭有无义突变，PKD 1：p.R4228X，出现在儿子从头，简单的囊肿可能解释了母亲的表型。在西班牙家族中未发现可能的突变，但在1例病例中表现为非典型肾萎缩。因此，重新分析不支持ADPKD中存在PKD 3。在所有已解决的家族中，超声诊断的假阳性显示了突变筛查的价值，但不是连锁，以了解具有不一致数据的家族。
Mutations to PKD1 and PKD2 are associated with autosomal dominant polycystic kidney disease (ADPKD). The absence of apparent PKD1/PKD2 linkage in five published European or North American families with ADPKD suggested a third locus, designated PKD3. Here we re-evaluated these families by updating clinical information, re-sampling where possible, and mutation screening for PKD1/PKD2. In the French-Canadian family we identified PKD1: p.D3782_V3783insD, with misdiagnoses in two individuals and sample contamination explaining the lack of linkage. In the Portuguese family, PKD1: p.G3818A segregated with the disease in 10 individuals in three generations with likely misdiagnosis in one individual, sample contamination, and use of distant microsatellite markers explaining the linkage discrepancy. The mutation, PKD2: c.213delC, was found in the Bulgarian family, with linkage failure attributed to false positive diagnoses in two individuals. An affected son but not the mother, in the Italian family had the nonsense mutation, PKD1: p.R4228X, which appeared de novo in the son; with simple cysts probably explaining the mother’s phenotype. No likely mutation was found in the Spanish family, but the phenotype was atypical with kidney atrophy in one case. Thus, re-analysis does not support the existence of a PKD3 in ADPKD. False positive diagnoses by ultrasound in all resolved families shows the value of mutation screening, but not linkage, to understand families with discrepant data.
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