{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:26:44Z","timestamp":1761514004804,"version":"3.40.5"},"reference-count":0,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2017,5,12]],"date-time":"2017-05-12T00:00:00Z","timestamp":1494547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2017,5,12]],"date-time":"2017-05-12T00:00:00Z","timestamp":1494547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroendocrinology"],"published-print":{"date-parts":[[2018]]},"abstract":"<b><i>Background\/Aim:<\/i><\/b> Variability in the severity and age at onset of autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) may be associated with certain types of variants in the arginine vasopressin (<i>AVP<\/i>) gene. In this study, we aimed to describe a large family with an apparent predominant female occurrence of polyuria and polydipsia and to determine the underlying cause. <b><i>Methods:<\/i><\/b> The family members reported their family demography and symptoms. Two subjects were diagnosed by fluid deprivation and dDAVP challenge tests. Eight subjects were tested genetically. The identified variant along with 3 previously identified variants in the <i>AVP<\/i> gene were investigated by heterologous expression in a human neuronal cell line (SH-SY5Y). <b><i>Results:<\/i><\/b> Both subjects investigated clinically had a partial neurohypophyseal diabetes insipidus phenotype. A g.276_278delTCC variant in the <i>AVP<\/i> gene causing a Ser18del deletion in the signal peptide (SP) of the AVP preprohormone was perfectly co-segregating with the disease. When expressed in SH-SY5Y cells, the Ser18del variant along with 3 other SP variants (g.227G>A, Ser17Phe, and Ala19Thr) resulted in reduced <i>AVP<\/i> mRNA, impaired AVP secretion, and partial AVP prohormone degradation and retention in the endoplasmic reticulum. Impaired SP cleavage was demonstrated directly in cells expressing the Ser18del, g.227G>A, and Ala19Thr variants, using state-of-the-art mass spectrometry. <b><i>Conclusion:<\/i><\/b> Variants affecting the SP of the AVP preprohormone cause adFNDI with variable phenotypes by a mechanism that may involve impaired SP cleavage combined with effects at the mRNA, protein, and cellular level.<\/jats:p>","DOI":"10.1159\/000477246","type":"journal-article","created":{"date-parts":[[2017,5,11]],"date-time":"2017-05-11T21:03:22Z","timestamp":1494536602000},"page":"167-186","source":"Crossref","is-referenced-by-count":13,"title":["The Novel Ser18del AVP Variant Causes Inherited Neurohypophyseal Diabetes Insipidus by Mechanisms Shared with Other Signal Peptide Variants"],"prefix":"10.1159","volume":"106","author":[{"given":"Lise Bols","family":"Toustrup","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helene","family":"Kvistgaard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"Palmfeldt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte Kj\u00e6r","family":"Bjerre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels","family":"Gregersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00f8ren","family":"Rittig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3588-6350","authenticated-orcid":false,"given":"Thomas Juhl","family":"Corydon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane H.","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2017,5,12]]},"container-title":["Neuroendocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/477246","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/477246","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:27:41Z","timestamp":1745425661000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000477246"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,12]]},"references-count":0,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2018,2,22]]},"published-print":{"date-parts":[[2018,2,6]]}},"URL":"https:\/\/doi.org\/10.1159\/000477246","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.5107561","asserted-by":"subject"}]},"ISSN":["0028-3835","1423-0194"],"issn-type":[{"type":"print","value":"0028-3835"},{"type":"electronic","value":"1423-0194"}],"subject":[],"published":{"date-parts":[[2017,5,12]]}}}