Evidence of oligogenic inheritance in nephronophthisis
Evidence of oligogenic inheritance in nephronophthisis
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DOI：
10.1681/asn.2007020243
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发表时间：
2007-10-01
影响因子：
13.6
通讯作者：
Hildebrandt, Friedhelm
中科院分区：
文献类型：
--
作者：
Hoefele, Julia;Wolf, Matthias T. F.;Hildebrandt, Friedhelm
肾病是一种隐性囊性肾脏疾病，可在生命的前20年导致终末期肾衰竭。25%的肾病病例是由NPHP1的大量纯合缺失引起的，但是已经确定了6个与肾病有关的基因。由于低基因遗传已被描述为相关的Bardet-Biedl综合征，我们评估了是否在肾病病例中也可以检测到多个基因的突变。由于已知肾囊素1至4具有相互作用，我们研究了来自94个不同家族的肾病患者，并对NPHP1、NPHP2、NPHP3和NPHP4基因的所有外显子进行了测序。在我们之前涉及44个家族的研究中，我们检测到NPHP1-4基因中的一个发生了两个突变。在这里，我们在六个家族中检测到NPHP1、NPHP3或NPHP4的两个突变，并在其他一个NPHP基因中发现了第三个突变。此外，我们通过检测一名携带NPHP2突变和NPHP3突变的个体，发现了可能的遗传性疾病。最后，我们在9个家族中检测到单个突变的存在，这表明第二个隐性突变可能在另一个尚未确定的NPHP基因中。我们的研究结果表明，少原性可能发生在肾肾病病例中。
Nephronophthisis is a recessive cystic renal disease that leads to end-stage renal failure in the first two decades of life. Twenty-five percent of nephronophthisis cases are caused by large homozygous deletions of NPHP1, but six genes responsible for nephronophthisis have been identified. Because oligogenic inheritance has been described for the related Bardet-Biedl syndrome, we evaluated whether mutations in more than one gene may also be detected in cases of nephronophthisis. Because the nephrocystins 1 to 4 are known to interact, we examined patients with nephronophthisis from 94 different families and sequenced all exons of the NPHP1, NPHP2, NPHP3, and NPHP4 genes. In our previous studies involving 44 families, we detected two mutations in one of the NPHP1-4 genes. Here, we detected in six families two mutations in either NPHP1, NPHP3, or NPHP4, and identified a third mutation in one of the other NPHP genes. Furthermore, we found possible digenic disease by detecting one individual who carried one mutation in NPHP2 and a second mutation in NPHP3. Finally, we detected the presence of a single mutation in nine families, suggesting that the second recessive mutation may be in another as yet unidentified NPHP gene. Our findings suggest that oligogenicity may occur in cases of nephronophthisis.