Novel AVPR2 mutation causing partial nephrogenic diabetes insipidus in a Japanese family
Novel AVPR2 mutation causing partial nephrogenic diabetes insipidus in a Japanese family
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DOI：
10.1515/jpem-2015-0323
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发表时间：
2016-05-01
影响因子：
1.4
通讯作者：
Hata, Daisuke
中科院分区：
文献类型：
--
作者：
Yamashita, Sumie;Hata, Astuko;Hata, Daisuke
背景资料：X连锁隐性遗传性先天性肾源性尿崩症（NDI）是由精氨酸加压素2型受体基因（AVPR 2）突变引起的。超过200个突变的AVPR2基因与完整的NDI已被报道，虽然只有15个突变与部分NDI已被报道到data.Methods：我们在此报告一个日本亲属与部分NDI。先证者是一个8岁的男孩谁被转介到我们医院夜间遗尿症。结果：基因组DNA检测发现一种新的错义突变（p.L161P）。病人的母亲是突变的杂合子。三维模型研究表明，L161 P可能使V2受体跨膜区失稳，导致其错误折叠或错误定位。结论：NDI与遗尿症的鉴别具有重要意义。诊断部分NDI的临床线索是尽管血清渗透压正常，但AVP水平不相容地高。
Background: X-linked recessive congenital nephrogenic diabetes insipidus (NDI) is caused by mutations of the arginine vasopressin type 2 receptor gene (AVPR2). More than 200 mutations of the AVPR2 gene with complete NDI have been reported although only 15 mutations with partial NDI has been reported to date.Methods: We herein report a Japanese kindred with partial NDI. The proband is an 8-year-old boy who was referred to our hospital for nocturnal enuresis. Water deprivation test and hypertonic saline test suggested partial renal antidiuretic hormone arginine vasopressin (AVP) resistance.Results: Analysis of genomic DNA revealed a novel missense mutation (p.L161P) in the patient. The patient's mother was heterozygous for the mutation. Three-dimensional (3-D) modeling study showed that L161P possibly destabilizes the transmembrane domain of the V2 receptor, resulting in its misfolding or mislocalization.Conclusions: Distinguishing partial NDI from nocturnal enuresis is important. A clinical clue for diagnosis of partial NDI is an incompatibly high level of AVP despite normal serum osmolality.