Abstract：
Nephrogenic diabetes insipidus (NDI) is a rare genetic disorder primarily associated with mutations in the arginine vasopressin receptor 2 (AVPR2) gene or the aquaporin 2 (AQP2) gene, resulting in impaired water reabsorption in the renal tubules. This report describes a case of a young male patient with NDI from China with a history of polydipsia and polyuria for over 15 years. Laboratory examinations of the proband indicated low urine-specific gravity and osmolality. Urologic ultrasound revealed severe bilateral hydronephrosis in both kidneys, bilateral dilatation of the ureters, roughness of the bladder wall, and the formation of muscle trabeculae. The diagnosis of diabetes insipidus was confirmed by water deprivation tests. The administration of posterior pituitary hormone did not alter urine-specific gravity, and osmolality remained at a low level (<300 mOsm/kg). Based on these findings, and the genetic tests of the proband and his parents were performed. A missense mutation (c.616 G>C) in exon 3 of the AVPR2 gene of the proband was found, caused by the substitution of amino acid valine to leucine at position 206 [p.Val206Leu], which was a hemizygous mutation and consistent with X-chromosome recessive inheritance. The administration of oral hydrochlorothiazide improves the symptoms of polydipsia and polyuria in the proband. This novel AVPR2 gene mutation may be the main cause of NDI in this family, which induces a functional defect in AVPR2, and leads to reduced tubular reabsorption of water.
摘要：
肾源性尿崩症（NDI）是一种罕见的遗传性疾病，主要与精氨酸加压素受体2（AVPR2）基因或水通道蛋白2（AQP2）基因突变有关。导致肾小管中水的重吸收受损。本报告描述了一名来自中国的年轻男性NDI患者，该患者有超过15年的多饮和多尿病史。先证者的实验室检查表明尿液比重和渗透压较低。泌尿外科超声显示双肾严重双侧肾积水，输尿管双侧扩张，膀胱壁的粗糙度，和肌肉小梁的形成。通过水剥夺试验证实了尿崩症的诊断。给予垂体后叶激素不会改变尿液比重，和渗透压保持在低水平(<300mOsm/kg)。基于这些发现,并对先证者及其父母进行了基因测试。在先证者的AVPR2基因外显子3中发现了一个错义突变（c.616G>C），由氨基酸缬氨酸取代为206位的亮氨酸引起[p。Val206Leu],这是一种半合子突变，与X染色体隐性遗传一致。口服氢氯噻嗪可改善先证者的多饮和多尿症状。这种新的AVPR2基因突变可能是该家族NDI的主要原因,这会引起AVPR2的功能缺陷，并导致肾小管对水的重吸收减少。
