A case of nephrogenic diabetes insipidus with a novel missense mutation in the AVPR2 gene
A case of nephrogenic diabetes insipidus with a novel missense mutation in the AVPR2 gene
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DOI：
10.1007/s00467-006-0388-8
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发表时间：
2007-05-01
影响因子：
3
通讯作者：
Tamai, Hiroshi
中科院分区：
文献类型：
--
作者：
Ashida, Akira;Yamamoto, Daisuke;Tamai, Hiroshi
我们描述了一个儿科病例的肾源性尿崩症（NDI）与一个新的错义突变精氨酸加压素受体2（AVPR 2）基因。患者为一名3岁男孩，有多尿（4357 ml/天，7230 ml/m2/天）和烦渴。禁水试验表明尿量无减少，皮下注射0.1 U/kg匹加压素对尿量无反应。分子遗传学分析表明，患者有一个AVPR 2错义突变，涉及取代苯丙氨酸酪氨酸在位置205（Y205 F）。还发现患者的母亲是该Y205 F突变的杂合子。通过分子模拟分析Tyr-205氢基团的分子间相互作用表明，Tyr-205位于跨膜结构域（TM）5中，其羟基与位于TM 4中的Leu-169主链=O形成氢键。Tyr-205突变为苯丙氨酸会导致这种氢键的丧失，并降低或改变这些TM螺旋之间的相互作用，从而影响AVP与受体结合的能力。根据AVPR 2的分子模型，Y205 F突变会导致肾源性尿崩症。
We describe a pediatric case of nephrogenic diabetes insipidus (NDI) with a novel missense mutation in the arginine vasopressin receptor 2 (AVPR2) gene. The patient, a 3-year-old boy, had polyuria (4357 ml/day, 7230 ml/m(2) /day) and polydipsia. Water deprivation testing demonstrated no decrease of urine volume, and urinary volume did not respond to subcutaneous injection of 0.1 U/kg pitressin. Molecular genetic analysis demonstrated that the patient had an AVPR2 missense mutation involving substitution of phenylalanine for tyrosine at position 205 (Y205F). It was also found that the patient's mother was heterozygous for this Y205F mutation. Analysis of the intermolecular interaction of the Tyr-205 hydrogen group by molecular modeling showed that Tyr-205 was located in transmembrane domain (TM) 5, and that its hydroxy group formed a hydrogen bond with Leu-169 main-chain =O located in TM 4. The mutation of Tyr-205 to phenylalanine would cause loss of this hydrogen bond and decrease or change the interaction between these TM coils, thus affecting the ability of AVP to bind to the receptor. According to this molecular model of AVPR2, the Y205F mutation would cause nephrogenic diabetes insipidus.