Autosomal Dominant Mutation in the Signal Peptide of Renin in a Kindred With Anemia, Hyperuricemia, and CKD
Autosomal Dominant Mutation in the Signal Peptide of Renin in a Kindred With Anemia, Hyperuricemia, and CKD
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DOI：
10.1053/j.ajkd.2011.06.029
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发表时间：
2011-11-01
影响因子：
13.2
通讯作者：
Wolf, Matthias T. F.
中科院分区：
文献类型：
--
作者：
Beck, Bodo B.;Trachtman, Howard;Wolf, Matthias T. F.
肾素（REN）纯合或复合杂合突变会导致肾小管发育不全，其特征是由于肾衰竭和肺发育不全而导致子宫内死亡。该表型类似于妊娠期间服用血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂引起的胎儿病。最近，杂合 REN 突变被证明会导致早发性高尿酸血症、贫血和慢性肾脏病 (CKD)。迄今为止，仅发表了 3 种不同的杂合 REN 突变。我们报告了 39 个患有高尿酸血症和 CKD 家族的 REN 基因突变分析，这些家族之前的 UMOD（尿调节蛋白）和 HNF1B（肝细胞核因子 1 β）基因突变检测呈阴性。我们鉴定出一种在 REN 互补 DNA 的第 28 位具有新的胸苷至胞嘧啶突变的亲族，对应于氨基酸 10 处的色氨酸至精氨酸的取代，该突变存在于信号序列中 (c.28T>C; p.W10R)。在此基础上，我们得出结论，REN 突变在 CKD 患者中是罕见事件。在亲属中，我们发现 4 代以上的受影响个体携带新的 REN 突变，并以严重贫血、高尿酸血症和 CKD 为特征。贫血严重且与肾功能下降的程度不成比例。由于已描述的所有杂合 REN 突变均位于信号序列中，因此对患有高尿酸血症和贫血的 CKD 患者进行 REN 基因筛查最好集中于编码信号肽的外显子 1 的测序。 Am J 肾病杂志。 58（5）：821-825。由 Elsevier Inc. 代表国家肾脏基金会 (National Kidney Foundation, Inc.) 出版。这是美国政府的作品。其使用没有任何限制。
Homozygous or compound heterozygous mutations in renin (REN) cause renal tubular dysgenesis, which is characterized by death in utero due to kidney failure and pulmonary hypoplasia. The phenotype resembles the fetopathy caused by angiotensin-converting enzyme inhibitor or angiotensin receptor blocker intake during pregnancy. Recently, heterozygous REN mutations were shown to result in early-onset hyperuricemia, anemia, and chronic kidney disease (CKD). To date, only 3 different heterozygous REN mutations have been published. We report mutation analysis of the REN gene in 39 kindreds with hyperuricemia and CKD who previously tested negative for mutations in the UMOD (uromodulin) and HNF1B (hepatocyte nuclear factor 1 beta) genes. We identified one kindred with a novel thymidine to cytosine mutation at position 28 in the REN complementary DNA, corresponding to a tryptophan to arginine substitution at amino acid 10, which is found within the signal sequence (c.28T>C; p.W10R). On this basis, we conclude that REN mutations are rare events in patients with CKD. Within the kindred, we found affected individuals over 4 generations who carried the novel REN mutation and were characterized by significant anemia, hyperuricemia, and CKD. Anemia was severe and disproportional to the degree of decreased kidney function. Because all heterozygous REN mutations that have been described are localized in the signal sequence, screening of the REN gene for patients with CKD with hyperuricemia and anemia may best be focused on sequencing of exon 1, which encodes the signal peptide. Am J Kidney Dis. 58(5):821-825. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use.