Intrafamilial phenotype variability in nephrogenic diabetes insipidus.
Intrafamilial phenotype variability in nephrogenic diabetes insipidus.
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肾性尿崩症的家族内表型变异。
DOI：
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发表时间：
2002
影响因子：
13.2
通讯作者：
O. Devuyst
中科院分区：
文献类型：
--
作者：
Karine Kalenga;A. Persu;É. Goffin;E. Lavenne;P. V. Van Cangh;D. Bichet;O. Devuyst
x连锁肾源性尿崩症（NDI）占遗传性NDI病例的90%，是由编码精氨酸抗利尿素（AVP）受体2型（V2R）的AVPR2基因突变引起的。V2R介导AVP在集管主要细胞中的抗利尿作用。迄今为止，只有三种AVPR2突变（P322S， D85N和G201D）与轻度NDI表型相关，并且在受影响的男性中尚未报道家族内表型变异性。我们描述了一个新的比利时家族，其x连锁NDI是由AVPR2的137位（R137H）的组氨酸取代精氨酸引起的。这种突变已经在两个兄弟和他们的母亲身上被发现。R137H突变导致V2R不能刺激腺苷酸环化酶，并与严重的NDI和在缺水和/或输注1-去氨氨基-8-d-精氨酸加压素时尿液渗透压不能增加到大于血浆渗透压相关。对两名受影响的兄弟的详细检查显示，45岁的先证者具有典型的NDI表型，而33岁的兄弟的临床表型较轻，与缺水期间显著的尿浓缩能力相关。因此，在这个家族中，R137H突变与轻度或重度NDI表型相关。可能解释这些发现的机制包括遗传和/或环境修饰因素。
X-Linked nephrogenic diabetes insipidus (NDI), which accounts for 90% of inherited cases of NDI, is caused by mutations in the AVPR2 gene that encodes the arginine vasopressin (AVP) receptor type 2 (V2R). The V2R mediates the antidiuretic action of AVP in principal cells of the collecting duct. To date, only three AVPR2 mutations (P322S, D85N, and G201D) have been associated with a mild NDI phenotype, and intrafamilial phenotype variability has not been reported in affected males. We describe a novel Belgian family with X-linked NDI caused by substitution of a histidine for an arginine at position 137 (R137H) of AVPR2. This mutation has been identified in two brothers and their mother. The R137H mutation results in a failure of V2R to stimulate adenylate cyclase and has been associated consistently with severe NDI and the inability to increase urinary osmolality to greater than plasma osmolality during water deprivation and/or infusion of 1-desamino-8-d-arginine vasopressin. Detailed examination of the two affected brothers showed the typical NDI phenotype in the 45-year-old proband, whereas a milder clinical phenotype associated with significant urinary concentrating ability during water deprivation was documented in the 33-year-old brother. Thus, in this family, the R137H mutation is associated with either a mild or severe NDI phenotype. Mechanisms that might account for these findings include genetic and/or environmental modifiers.
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影响因子：
--
作者：
Heydar Sadeghi;Gary L. Robertson;D. Bichet;Giulio Innamorati;Mariel Birnbaumer
通讯作者：
Heydar Sadeghi;Gary L. Robertson;D. Bichet;Giulio Innamorati;Mariel Birnbaumer
DOI：
10.1073/pnas.85.22.8459
发表时间：
1988-11-01
影响因子：
11.1
作者：
KARNIK, SS;SAKMAR, TP;KHORANA, HG
通讯作者：
KHORANA, HG
DOI：
10.1073/pnas.98.1.93
发表时间：
2001-01
影响因子：
11.1
作者：
L. Barak;R. Oakley;S. Laporte;M. G. Caron
通讯作者：
L. Barak;R. Oakley;S. Laporte;M. G. Caron
筛查有中枢性先天性通气不足综合征家族史的儿童。
影响因子：
0.9
作者：
Emanuel,Hina;Rennie,Kimberly;Macdonald,Kelly;Yadav,Aravind;Mosquera,RicardoA
通讯作者：
Mosquera,RicardoA
DOI：
10.1042/bj2830001
发表时间：
1992-04
期刊：
The Biochemical journal
影响因子：
--
作者：
T. Savarese;Claire-M. FRASERt
通讯作者：
T. Savarese;Claire-M. FRASERt