Lacoste Mireille, Cai Yi, Guicharnaud Liliane, Mounier Françoise, Dumez Yves, Bouvier Raymonde, Dijoud Frédérique, Gonzales Marie, Chatten Jane, Delezoide Anne-Lise, Daniel Laurent, Joubert Madeleine, Laurent Nicole, Aziza Jacqueline, Sellami Tahya, Amar Hatem Ben, Jarnet Catherine, Frances Anne Marie, Daïkha-Dahmane Farida, Coulomb Aurore, Neuhaus Thomas J, Foliguet Bernard, Chenal Pierre, Marcorelles Pascale, Gasc Jean Marie, Corvol Pierre, Gubler Marie Claire
Institut National de la Santé et de la Recherche Médicale, Unité 574, Collège de France, Paris, France.
J Am Soc Nephrol. 2006 Aug;17(8):2253-63. doi: 10.1681/ASN.2005121303. Epub 2006 Jun 21.
Renal tubular dysgenesis is a clinical disorder that is observed in fetuses and characterized by the absence or poor development of proximal tubules, early onset and persistent oligohydramnios that leads to the Potter sequence, and skull ossification defects. It may be acquired during fetal development or inherited as an autosomal recessive disease. It was shown recently that autosomal recessive renal tubular dysgenesis is genetically heterogeneous and linked to mutations in the genes that encode components of the renin-angiotensin system. This study analyzed the clinical expression of the disease in 29 fetus/neonates from 18 unrelated families and evaluated changes in renal morphology and expression of the renin-angiotensin system. The disease was uniformly severe, with perinatal death in all cases as a result of persistent anuria and hypoxia related to pulmonary hypoplasia. Severe defects in proximal tubules were observed in all fetuses from 18 gestational weeks onward, and lesions also involved other tubular segments. They were associated with thickening of the renal arterial vasculature, from the arcuate to the afferent arteries. Renal renin expression was strikingly increased in 19 of 24 patients studied, from 13 families, whereas no renal renin was detected in four patients from three families. Angiotensinogen and angiotensin-converting enzyme were absent or present in only small amounts in the proximal tubule, in correlation with the severity of tubular abnormalities. No specific changes were detected in angiotensin II receptor expression. The severity and the early onset of the clinical and pathologic expression of the disease underline the major importance of this system in fetal kidney function and development in humans. The identification of the disease on the basis of precise histologic analysis and the research of the genetic defect now allow genetic counseling and early prenatal diagnosis.
肾小管发育不全是一种在胎儿中观察到的临床病症，其特征为近端小管缺失或发育不良、早发且持续性羊水过少导致波特序列征以及颅骨骨化缺陷。它可能在胎儿发育过程中获得，或作为常染色体隐性疾病遗传。最近研究表明，常染色体隐性肾小管发育不全在遗传上具有异质性，且与编码肾素 - 血管紧张素系统成分的基因突变有关。本研究分析了来自18个无亲缘关系家庭的29例胎儿/新生儿中该疾病的临床表型，并评估了肾脏形态变化以及肾素 - 血管紧张素系统的表达情况。该疾病均表现严重，所有病例均因持续性无尿和与肺发育不全相关的缺氧而在围产期死亡。从妊娠18周起，在所有胎儿中均观察到近端小管严重缺陷，病变还累及其他肾小管节段。这些病变与从弓形动脉到入球小动脉的肾动脉血管系统增厚有关。在来自13个家庭的24例研究患者中，有19例肾素表达显著增加，而来自3个家庭的4例患者未检测到肾素。血管紧张素原和血管紧张素转换酶在近端小管中缺失或仅少量存在，这与肾小管异常的严重程度相关。在血管紧张素II受体表达方面未检测到特异性变化。该疾病临床和病理表现的严重性及早发性突显了该系统在人类胎儿肾功能和发育中的重要作用。基于精确的组织学分析对该疾病进行识别以及对遗传缺陷的研究，现在使得遗传咨询和早期产前诊断成为可能。
