Novel and recurrent variants in AVPR2 in 19 families with X-linked congenital nephrogenic diabetes insipidus

被引:18
作者
Joshi, Shivani [1 ,2 ]
Kvistgaard, Helene [1 ,2 ]
Kamperis, Konstantinos [1 ,2 ]
Faerch, Mia [1 ,2 ]
Hagstrom, Soren [3 ]
Gregersen, Niels [4 ]
Rittig, Soren [1 ,2 ]
Christensen, Jane Hvarregaard [1 ,2 ,5 ]
机构
[1] Aarhus Univ Hosp, Dept Pediat & Adolescent Med, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark
[2] Aarhus Univ Hosp, Dept Clin Med, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark
[3] Aalborg Univ Hosp, Dept Pediat, Reberbansgade 15, DK-9000 Aalborg, Denmark
[4] Dept Clin Med, Res Unit Mol Med, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark
[5] Aarhus Univ, Dept Biomed, Bartholins Alle 6, DK-8000 Aarhus C, Denmark
关键词
X-linked CNDI; AVPR2; Novel variants; Genetic testing; VASOPRESSIN TYPE-2 RECEPTOR; MUTATIONS; GENE;
D O I
10.1007/s00431-018-3132-z
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Congenital nephrogenic diabetes insipidus (CNDI) is characterized by the reduced ability of renal collecting duct cells to reabsorb water in response to the antidiuretic effect of vasopressin. Chronic polyuria and polydipsia are the hallmarks of the disease. Approximately 90% of all patients with CNDI have X-linked inherited disease caused by variants in the arginine vasopressin receptor 2 (AVPR2) gene. We present genetic findings in 34 individuals from 19 kindreds including one or more family members with CNDI. Coding regions of AVPR2 were sequenced bi-directionally. We identified eight novel disease-causing variants in AVPR2, p.Arg68Alafs*124, p.Ser171Arg, p.Gln174Pro, p.Trp200Arg, p.Gly201Cys, p.Gly220Arg, p.Val226Glu, and p.Gln291Pro in nine kindreds. In all three families with more than one affected individual, the novel variants segregated with the disease. We also identified eight recurrent disease-causing variants, p.Val88Met, p.Leu111Valfs*80, p.Arg113Trp, p.Tyr124*, p.Ser167Leu, p.Thr207Asn, p.Arg247Alafs*12, and p.Arg337* in ten kindreds. Our findings contribute to the growing list of AVPR2 variants causing X-linked CNDI. Conclusion: Being a rapid diagnostic tool for CNDI, direct sequencing of AVPR2 should be encouraged in newborns with familial predisposition to CNDI.
引用
收藏
页码:1399 / 1405
页数:7
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