{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T02:23:17Z","timestamp":1794190997754,"version":"4.8.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Appl Genetics"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1007\/s13353-025-01027-6","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T01:32:50Z","timestamp":1762133570000},"page":"1113-1118","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Familial hyponatremia conditioned by the R137C mutation with constitutive activation of the vasopressin receptor"],"prefix":"10.1007","volume":"67","author":[{"given":"Hanna","family":"Szymanik-Grzelak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6525-0882","authenticated-orcid":false,"given":"Maria","family":"Daniel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Pa\u0144czyk-Tomaszewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"issue":"5","key":"1027_CR1","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1007\/s00467-018-3922-6","volume":"34","author":"F Bardanzellu","year":"2019","unstructured":"Bardanzellu F, Pintus MC, Masile V, Fanos V, Marcialis MA (2019) Focus on neonatal and infantile onset of nephrogenic syndrome of inappropriate antidiuresis: 12 years later. Pediatr Nephrol 34(5):763\u2013775","journal-title":"Pediatr Nephrol"},{"issue":"3","key":"1027_CR2","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s00467-006-0344-7","volume":"22","author":"DF Bes","year":"2007","unstructured":"Bes DF, Mendilaharzu H, Fenwick RG, Arrizurieta E (2007) Hyponatremia resulting from arginine vasopressin receptor 2 gene mutation. Pediatr Nephrol 22(3):463\u2013466","journal-title":"Pediatr Nephrol"},{"issue":"4","key":"1027_CR3","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1053\/j.ajkd.2011.09.026","volume":"59","author":"D Bockenhauer","year":"2012","unstructured":"Bockenhauer D, Penney MD, Hampton D, van\u2019t Hoff W, Gullett A, Sailesh S, Bichet DG (2012) A family with hyponatremia and the nephrogenic syndrome of inappropriate antidiuresis. Am J Kidney Dis 59(4):566\u2013568","journal-title":"Am J Kidney Dis"},{"issue":"1","key":"1027_CR4","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1159\/000381586","volume":"84","author":"C Brachet","year":"2015","unstructured":"Brachet C, Vandergheynst F, Heinrichs C (2015) Nephrogenic syndrome of inappropriate antidiuresis in a female neonate: review of the clinical presentation in females. Horm Res Paediatr 84(1):65\u201367","journal-title":"Horm Res Paediatr"},{"issue":"7","key":"1027_CR5","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.arcped.2017.04.013","volume":"24","author":"A Cailleaux","year":"2017","unstructured":"Cailleaux A, Mahieu F, Heinrichs C, Adams B, Ismaili K, Brachet C (2017) Nephrogenic syndrome of inappropriate antidiuresis: early diagnosis avoids severe hyponatremia complications. Arch Pediatr 24(7):630\u2013633","journal-title":"Arch Pediatr"},{"issue":"10","key":"1027_CR6","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1681\/ASN.2012010077","volume":"23","author":"E Carpentier","year":"2012","unstructured":"Carpentier E, Greenbaum LA, Rochdi D, Abrol R, Goddard WA 3rd, Bichet DG, Bouvier M (2012) Identification and characterization of an activating F229V substitution in the V2 vasopressin receptor in an infant with NSIAD. J Am Soc Nephrol 23(10):1635\u20131640","journal-title":"J Am Soc Nephrol"},{"key":"1027_CR7","doi-asserted-by":"crossref","unstructured":"Cheung CC, Cadnapaphornchai MA, Ranadive SA, Gitelman SE, Rosenthal SM (2012) Persistent elevation of urine aquaporin-2 during water loading in a child with nephrogenic syndrome of inappropriate antidiuresis (NSIAD) caused by a R137L mutation in the V2 vasopressin receptor. Int J Pediatr Endocrinol 2012(1):3","DOI":"10.1186\/1687-9856-2012-3"},{"key":"1027_CR8","doi-asserted-by":"crossref","unstructured":"Cho YH, Gitelman S, Rosenthal S, Ambler G (2009) Long-term outcomes in a family with nephrogenic syndrome of inappropriate antidiuresis. Int J Pediatr Endocrinol. 2009:1\u20134","DOI":"10.1155\/2009\/431527"},{"issue":"2","key":"1027_CR9","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1681\/ASN.2006090987","volume":"18","author":"G Decaux","year":"2007","unstructured":"Decaux G, Vandergheynst F, Bouko Y, Parma J, Vassart G, Vilain C (2007) Nephrogenic syndrome of inappropriate antidiuresis in adults: high phenotypic variability in men and women from a large pedigree. J Am Soc Nephrol 18(2):606\u2013612","journal-title":"J Am Soc Nephrol"},{"key":"1027_CR10","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1173601","volume":"14","author":"LS Erd\u00e9lyi","year":"2023","unstructured":"Erd\u00e9lyi LS, Hunyady L, Balla A (2023) V2 vasopressin receptor mutations: future personalized therapy based on individual molecular biology. Front Endocrinol (Lausanne) 14:1173601","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"5","key":"1027_CR11","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1038\/ki.2015.181","volume":"88","author":"LS Erd\u00e9lyi","year":"2015","unstructured":"Erd\u00e9lyi LS, Mann WA, Morris-Rosendahl DJ, Gro\u00df U, Nagel M, V\u00e1rnai P et al (2015) Mutation in the V2 vasopressin receptor gene, AVPR2, causes nephrogenic syndrome of inappropriate diuresis. Kidney Int 88(5):1070\u20131078","journal-title":"Kidney Int"},{"issue":"18","key":"1027_CR12","doi-asserted-by":"publisher","first-page":"1884","DOI":"10.1056\/NEJMoa042743","volume":"352","author":"BJ Feldman","year":"2005","unstructured":"Feldman BJ, Rosenthal SM, Vargas GA, Fenwick RG, Huang EA, Matsuda-Abedini M et al (2005) Nephrogenic syndrome of inappropriate antidiuresis. N Engl J Med 352(18):1884\u20131890","journal-title":"N Engl J Med"},{"issue":"3","key":"1027_CR13","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1530\/EJE-09-0246","volume":"161","author":"S Gupta","year":"2009","unstructured":"Gupta S, Cheetham TD, Lambert HJ, Roberts C, Bourn D, Coulthard MG, Ball SG (2009) Thirst perception and arginine vasopressin production in a kindred with an activating mutation of the type 2 vasopressin receptor: the pathophysiology of nephrogenic syndrome of inappropriate antidiuresis. Eur J Endocrinol 161(3):503\u2013508","journal-title":"Eur J Endocrinol"},{"issue":"1","key":"1027_CR14","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.jpeds.2005.08.031","volume":"148","author":"EA Huang","year":"2006","unstructured":"Huang EA, Feldman BJ, Schwartz ID, Geller DH, Rosenthal SM, Gitelman SE (2006) Oral urea for the treatment of chronic syndrome of inappropriate antidiuresis in children. J Pediatr 148(1):128\u2013131","journal-title":"J Pediatr"},{"issue":"9","key":"1027_CR15","doi-asserted-by":"publisher","first-page":"2839","DOI":"10.1093\/ndt\/gfq324","volume":"25","author":"EN Levtchenko","year":"2010","unstructured":"Levtchenko EN (2010) Monnens LA (2010) Nephrogenic syndrome of inappropriate antidiuresis. Nephrol Dial Transplant 25(9):2839\u201343","journal-title":"Nephrol Dial Transplant"},{"issue":"2","key":"1027_CR16","doi-asserted-by":"publisher","first-page":"214","DOI":"10.4274\/jcrpe.galenos.2021.2021.0191","volume":"15","author":"J Mammadova","year":"2023","unstructured":"Mammadova J, Kara C, \u00c7elebi Bitkin E, \u0130zci G\u00fcll\u00fc E, Ayd\u0131n M (2023) Nephrogenic syndrome of inappropriate antidiuresis mimicking hyporeninemic hypoaldosteronism: case report of two infants. J Clin Res Pediatr Endocrinol 15(2):214\u2013219","journal-title":"J Clin Res Pediatr Endocrinol"},{"issue":"12","key":"1027_CR17","doi-asserted-by":"publisher","first-page":"2267","DOI":"10.1007\/s00467-008-0913-z","volume":"23","author":"MA Marcialis","year":"2008","unstructured":"Marcialis MA, Fa\u00e0 V, Fanos V, Puddu M, Pintus MC, Cao A, Rosatelli MC (2008) Neonatal onset of nephrogenic syndrome of inappropriate antidiuresis. Pediatr Nephrol 23(12):2267\u20132271","journal-title":"Pediatr Nephrol"},{"issue":"5","key":"1027_CR18","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1681\/ASN.2018121268","volume":"30","author":"M Miyado","year":"2019","unstructured":"Miyado M, Fukami M, Takada S, Terao M, Nakabayashi K, Hata K et al (2019) Germline-derived gain-of-function variants of Gs\u03b1-coding GNAS gene identified in nephrogenic syndrome of inappropriate antidiuresis. J Am Soc Nephrol 30(5):877\u2013889","journal-title":"J Am Soc Nephrol"},{"issue":"2","key":"1027_CR19","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1111\/cen.13011","volume":"85","author":"AS Powlson","year":"2016","unstructured":"Powlson AS, Challis BG, Halsall DJ, Schoenmakers E, Gurnell M (2016) Nephrogenic syndrome of inappropriate antidiuresis secondary to an activating mutation in the arginine vasopressin receptor AVPR2. Clin Endocrinol (Oxf) 85(2):306\u2013312","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"9","key":"1027_CR20","doi-asserted-by":"publisher","first-page":"E37","DOI":"10.1210\/jc.2009-2524","volume":"95","author":"B Ranchin","year":"2010","unstructured":"Ranchin B, Boury-Jamot M, Blanchard Gl, Dubourg L, Hadj-A\u00efssa A, Morin D et al (2010) Familial nephrogenic syndrome of inappropriate antidiuresis: dissociation between Aquaporin-2 and vasopressin excretion. J Clin Endocrinol Metab 95(9):E37\u2013E43","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"1027_CR21","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.3390\/cells9061354","volume":"9","author":"M Ranieri","year":"2020","unstructured":"Ranieri M, Venneri M, Pellegrino T, Centrone M, Di Mise A, Cotecchia S et al (2020) The vasopressin receptor 2 mutant R137L linked to the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) signals through an alternative pathway that increases AQP2 membrane targeting independently of S256 phosphorylation. Cells 9(6):1354","journal-title":"Cells"},{"issue":"5","key":"1027_CR22","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1124\/mol.109.061804","volume":"77","author":"MD Rochdi","year":"2010","unstructured":"Rochdi MD, Vargas GA, Carpentier E, Oligny-Longpr\u00e9 G, Chen S, Kovoor A et al (2010) Functional characterization of vasopressin type 2 receptor substitutions (R137H\/C\/L) leading to nephrogenic diabetes insipidus and nephrogenic syndrome of inappropriate antidiuresis: implications for treatments. Mol Pharmacol 77(5):836\u2013845","journal-title":"Mol Pharmacol"},{"issue":"10","key":"1027_CR23","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1093\/ndt\/gfae162","volume":"39","author":"G Spasovski","year":"2024","unstructured":"Spasovski G (2024) Hyponatraemia\u2014treatment standard 2024. Nephrol Dial Transplant 39(10):1583\u20131592","journal-title":"Nephrol Dial Transplant"},{"issue":"8","key":"1027_CR24","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1210\/me.2016-1002","volume":"30","author":"A Tiulpakov","year":"2016","unstructured":"Tiulpakov A, White CW, Abhayawardana RS, See HB, Chan AS, Seeber RM et al (2016) Mutations of vasopressin receptor 2 including novel L312S have differential effects on trafficking. Mol Endocrinol 30(8):889\u2013904","journal-title":"Mol Endocrinol"},{"key":"1027_CR25","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.cca.2021.05.006","volume":"519","author":"HF Tong","year":"2021","unstructured":"Tong HF, Leung MTS, Chan CHT, Cheung HN, Mak WLT, Chen PLS (2021) Nephrogenic syndrome of inappropriate antidiuresis - an ethnically, genetically and phenotypically diverse disorder: first report in a Chinese adult and review of published cases. Clin Chim Acta 519:214\u2013219","journal-title":"Clin Chim Acta"},{"issue":"3","key":"1027_CR26","doi-asserted-by":"publisher","first-page":"288","DOI":"10.4274\/jcrpe.4531","volume":"9","author":"G Tuli","year":"2017","unstructured":"Tuli G, Tessaris D, Einaudi S, De Sanctis L, Matarazzo P (2017) Tolvaptan treatment in children with chronic hyponatremia due to inappropriate antidiuretic hormone secretion: a report of three cases. J Clin Res Pediatr Endocrinol 9(3):288\u2013292","journal-title":"J Clin Res Pediatr Endocrinol"},{"issue":"3","key":"1027_CR27","doi-asserted-by":"publisher","first-page":"c168","DOI":"10.1159\/000338539","volume":"120","author":"F Vandergheynst","year":"2012","unstructured":"Vandergheynst F, Brachet C, Heinrichs C, Decaux G (2012) Long-term treatment of hyponatremic patients with nephrogenic syndrome of inappropriate antidiuresis: personal experience and review of published case reports. Nephron Clin Pract 120(3):c168\u2013c172","journal-title":"Nephron Clin Pract"},{"issue":"1","key":"1027_CR28","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/s00467-023-06091-w","volume":"39","author":"F Veligratli","year":"2024","unstructured":"Veligratli F, Alexandrou D, Shah S, Amin R, Dattani M, Gan HW et al (2024) Tolvaptan and urea in paediatric hyponatraemia. Pediatr Nephrol 39(1):177\u2013183","journal-title":"Pediatr Nephrol"},{"issue":"1","key":"1027_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-65996-w","volume":"10","author":"V Vezzi","year":"2020","unstructured":"Vezzi V, Ambrosio C, Gr\u00f2 MC, Molinari P, S\u00fcral G, Costa T et al (2020) Vasopressin receptor 2 mutations in the nephrogenic syndrome of inappropriate antidiuresis show different mechanisms of constitutive activation for G protein coupled receptors. Sci Rep 10(1):9111","journal-title":"Sci Rep"}],"container-title":["Journal of Applied Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13353-025-01027-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13353-025-01027-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13353-025-01027-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T01:39:09Z","timestamp":1794188349000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13353-025-01027-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["1027"],"URL":"https:\/\/doi.org\/10.1007\/s13353-025-01027-6","relation":{},"ISSN":["1234-1983","2190-3883"],"issn-type":[{"value":"1234-1983","type":"print"},{"value":"2190-3883","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,3]]},"assertion":[{"value":"30 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 August 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All procedures performed in studies involving human participants were in accordance with the institution\u2019s ethical standards and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from the participants\u2019 parents of the study.\u00a0This report does not contain any personal identifying information.\u00a0","order":2,"name":"Ethics","label":"Patient consent","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}