Spectrum of Mutations in the Renin-Angiotensin System Genes in Autosomal Recessive Renal Tubular Dysgenesis
Spectrum of Mutations in the Renin-Angiotensin System Genes in Autosomal Recessive Renal Tubular Dysgenesis
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DOI：
10.1002/humu.21661
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发表时间：
2012-02-01
期刊：
影响因子：
3.9
通讯作者：
Gubler, Marie Claire
中科院分区：
文献类型：
--
作者：
Gribouval, Olivier;Moriniere, Vincent;Gubler, Marie Claire
常染色体隐性遗传性肾小管发育不全（RTD）是一种严重的肾小管发育障碍，其特征是早发性和持续性胎儿无尿，导致羊水过少和Potter序列，与颅骨骨化缺陷相关。大多数病例的早期死亡是由于无尿、肺发育不全和顽固性动脉低血压。这种疾病与编码肾素-血管紧张素系统（RAS）几种组分的基因突变有关：AGT（血管紧张素原）、REN（肾素）、ACE（血管紧张素转换酶）和AGTR 1（血管紧张素II受体1型）。在这里，我们回顾了一系列的54个不同的突变，确定在48个无关的家庭。其中大多数是新的，ACE突变是最常见的，在三分之二的家庭（64.6%）中观察到。无论突变的基因是什么，临床过程的严重程度都是相似的，这强调了功能性RAS在人类胎儿生命期间维持血压和肾血流量的重要性。肾灌注不足，无论是遗传性的还是继发于各种疾病，都妨碍了近端小管的正常发育/分化。在精确的临床和组织学分析的基础上对疾病的鉴定以及对遗传缺陷的表征允许遗传咨询和早期产前诊断。Mutat 33：316-326，2012. (C)2011 Wiley Periodicals，Inc.
Autosomal recessive renal tubular dysgenesis (RTD) is a severe disorder of renal tubular development characterized by early onset and persistent fetal anuria leading to oligohydramnios and the Potter sequence, associated with skull ossification defects. Early death occurs in most cases from anuria, pulmonary hypoplasia, and refractory arterial hypotension. The disease is linked to mutations in the genes encoding several components of the renin-angiotensin system (RAS): AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), and AGTR1 (angiotensin II receptor type 1). Here, we review the series of 54 distinct mutations identified in 48 unrelated families. Most of them are novel and ACE mutations are the most frequent, observed in two-thirds of families (64.6%). The severity of the clinical course was similar whatever the mutated gene, which underlines the importance of a functional RAS in the maintenance of blood pressure and renal blood flow during the life of a human fetus. Renal hypoperfusion, whether genetic or secondary to a variety of diseases, precludes the normal development/differentiation of proximal tubules. The identification of the disease on the basis of precise clinical and histological analyses and the characterization of the genetic defects allow genetic counseling and early prenatal diagnosis. Hum Mutat 33:316-326, 2012. (C) 2011 Wiley Periodicals, Inc.