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Novel and recurrent variants in AVPR2 in 19 families with X-linked congenital nephrogenic diabetes insipidus.
Eur J Pediatr. 2018 Sep; 177(9):1399-1405.EJ

Abstract

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. What is Known: • Disease-causing variants in AVPR2 cause X-linked congenital nephrogenic diabetes insipidus (CNDI). • DNA sequencing of AVPR2 is rapid, facilitates differential diagnosis, early intervention, and genetic diagnosis thus reducing morbidity in CNDI. What is New: • 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, thereby adding to the growing list of AVPR2 disease-causing variants and emphasizing the importance of genetic testing in CNDI.

Authors+Show Affiliations

Department of Pediatrics and Adolescent Medicine and Department of Clinical Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.Department of Pediatrics and Adolescent Medicine and Department of Clinical Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.Department of Pediatrics and Adolescent Medicine and Department of Clinical Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.Department of Pediatrics and Adolescent Medicine and Department of Clinical Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.Department of Pediatrics, Aalborg University Hospital, Reberbansgade 15, 9000, Aalborg, Denmark.Department of Clinical Medicine - Research Unit for Molecular Medicine, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.Department of Pediatrics and Adolescent Medicine and Department of Clinical Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.Department of Pediatrics and Adolescent Medicine and Department of Clinical Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark. jhc@biomed.au.dk. Department of Biomedicine, Aarhus University, Bartholins Allé 6, 8000, Aarhus C, Denmark. jhc@biomed.au.dk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29594432

Citation

Joshi, Shivani, et al. "Novel and Recurrent Variants in AVPR2 in 19 Families With X-linked Congenital Nephrogenic Diabetes Insipidus." European Journal of Pediatrics, vol. 177, no. 9, 2018, pp. 1399-1405.
Joshi S, Kvistgaard H, Kamperis K, et al. Novel and recurrent variants in AVPR2 in 19 families with X-linked congenital nephrogenic diabetes insipidus. Eur J Pediatr. 2018;177(9):1399-1405.
Joshi, S., Kvistgaard, H., Kamperis, K., Færch, M., Hagstrøm, S., Gregersen, N., Rittig, S., & Christensen, J. H. (2018). Novel and recurrent variants in AVPR2 in 19 families with X-linked congenital nephrogenic diabetes insipidus. European Journal of Pediatrics, 177(9), 1399-1405. https://doi.org/10.1007/s00431-018-3132-z
Joshi S, et al. Novel and Recurrent Variants in AVPR2 in 19 Families With X-linked Congenital Nephrogenic Diabetes Insipidus. Eur J Pediatr. 2018;177(9):1399-1405. PubMed PMID: 29594432.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel and recurrent variants in AVPR2 in 19 families with X-linked congenital nephrogenic diabetes insipidus. AU - Joshi,Shivani, AU - Kvistgaard,Helene, AU - Kamperis,Konstantinos, AU - Færch,Mia, AU - Hagstrøm,Søren, AU - Gregersen,Niels, AU - Rittig,Søren, AU - Christensen,Jane Hvarregaard, Y1 - 2018/03/28/ PY - 2018/01/05/received PY - 2018/03/14/accepted PY - 2018/03/14/revised PY - 2018/3/30/pubmed PY - 2018/9/8/medline PY - 2018/3/30/entrez KW - AVPR2 KW - Genetic testing KW - Novel variants KW - X-linked CNDI SP - 1399 EP - 1405 JF - European journal of pediatrics JO - Eur. J. Pediatr. VL - 177 IS - 9 N2 - : 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. What is Known: • Disease-causing variants in AVPR2 cause X-linked congenital nephrogenic diabetes insipidus (CNDI). • DNA sequencing of AVPR2 is rapid, facilitates differential diagnosis, early intervention, and genetic diagnosis thus reducing morbidity in CNDI. What is New: • 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, thereby adding to the growing list of AVPR2 disease-causing variants and emphasizing the importance of genetic testing in CNDI. SN - 1432-1076 UR - https://www.unboundmedicine.com/medline/citation/29594432/Novel_and_recurrent_variants_in_AVPR2_in_19_families_with_X_linked_congenital_nephrogenic_diabetes_insipidus_ L2 - https://dx.doi.org/10.1007/s00431-018-3132-z DB - PRIME DP - Unbound Medicine ER -