{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:18:05Z","timestamp":1789010285282,"version":"build-2803163510"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Idiopathic early-onset central diabetes insipidus (CDI) might be due to mutations of arginine vasopressin\u2013neurophysin II (<jats:italic>AVP\u2013NPII<\/jats:italic> (<jats:italic>AVP<\/jats:italic>)) or wolframin (<jats:italic>WFS1<\/jats:italic>) genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and methods<\/jats:title><jats:p>Sequencing of <jats:italic>AVP<\/jats:italic> and <jats:italic>WFS1 <\/jats:italic>genes was performed in nine children with CDI, aged between 9 and 68 months, and negative family history for polyuria and polydipsia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two patients carried a mutation in the <jats:italic>AVP<\/jats:italic> gene: a heterozygous G-to-T transition at nucleotide position 322 of exon 2 (c.322G&gt;T) resulting in a stop codon at position 108 (p.Glu108X), and a novel deletion from nucleotide 52 to 54 (c.52_54delTCC) producing a deletion of a serine at position 18 (p.Ser18del) of the AVP pre-prohormone signal peptide. A third patient carried two heterozygous mutations in the <jats:italic>WFS1<\/jats:italic> gene localized on different alleles. The first change was A-to-G transition at nucleotide 997 in exon 8 (c.997A&gt;G), resulting in a valine residue at position 333 in place of isoleucine (p.Ile333Val). The second novel mutation was a 3\u200abp insertion in exon 8, c.2392_2393insACG causing the addition of an aspartate residue at position 797 and the maintenance of the correct open reading frame (p. Asp797_Val798insAsp). While similar WFS1 protein levels were detected in fibroblasts from healthy subjects and from the patient and his parents, a major sensitivity to staurosporine-induced apoptosis was observed in the patient fibroblasts as well as in patients with Wolfram syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Early-onset CDI is associated with<jats:italic> de novo <\/jats:italic>mutations of the <jats:italic>AVP<\/jats:italic> gene and with hereditary <jats:italic>WFS1<\/jats:italic> gene changes. These findings have valuable implications for management and genetic counseling.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-14-0942","type":"journal-article","created":{"date-parts":[[2015,3,5]],"date-time":"2015-03-05T02:14:29Z","timestamp":1425521669000},"page":"461-472","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":21,"title":["Early-onset central diabetes insipidus is associated with de novo arginine vasopressin\u2013neurophysin II or Wolfram syndrome 1 gene mutations"],"prefix":"10.1093","volume":"172","author":[{"given":"Silverio","family":"Perrotta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascia","family":"Di Iorgi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulvio Della","family":"Ragione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saverio","family":"Scianguetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Borriello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Elsa Maria","family":"Allegri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Ferraro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Santoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Napoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Calcagno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Giaccardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Cappa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carolina","family":"Salerno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Cozzolino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Maghnie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"14","key":"1_10481311","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1056\/NEJM200010053431403","volume":"343","author":"Maghnie","year":"2000","journal-title":"New England Journal of Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0028-4793","issn-type":"print"},{"key":"2_49919384","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1159\/000336333","volume":"77","year":"2012","journal-title":"HORMONE RESEARCH IN PEDIATRICS"},{"key":"3_49919385","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrendo.2011.100","volume":"7","year":"2011","journal-title":"NATURE REVIEWS ENDOCRINOLOGY"},{"issue":"1","key":"4_41709155","doi-asserted-by":"crossref","first-page":"e29150","DOI":"10.1371\/journal.pone.0029150","volume":"7","author":"Aloi","year":"2012","ISSN":"https:\/\/id.crossref.org\/issn\/1932-6203","issn-type":"print"},{"key":"5_49919386","first-page":"1264","volume":"99","year":"2013","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"4","key":"6_22626252","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1111\/j.1365-2265.2006.02616.x","volume":"65","author":"Maghnie","year":"2006","journal-title":"Clinical endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0300-0664","issn-type":"print"},{"issue":"4","key":"7_18128070","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.1210\/jc.2003-031608","volume":"89","author":"Maghnie","year":"2004","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"12","key":"8_41676470","doi-asserted-by":"publisher","first-page":"e28555","DOI":"10.1371\/journal.pone.0028555","volume":"6","author":"Borriello","year":"2011","ISSN":"https:\/\/id.crossref.org\/issn\/1932-6203","issn-type":"print"},{"issue":"3","key":"9_30304737","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1093\/carcin\/bgn010","volume":"29","year":"2008","journal-title":"Carcinogenesis","ISSN":"https:\/\/id.crossref.org\/issn\/0143-3334","issn-type":"print"},{"issue":"1","key":"10_39720359","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1530\/EJE-11-0048","volume":"165","year":"2011","journal-title":"European Journal of Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"},{"issue":"3","key":"11_17276675","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/S0379-0738(02)00289-X","volume":"129","author":"Morling","year":"2002","journal-title":"Forensic Science International","ISSN":"https:\/\/id.crossref.org\/issn\/1872-6283","issn-type":"print"},{"issue":"8-9","key":"12_19398728","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/j.exger.2005.06.008","volume":"40","author":"Philbrook","year":"2005","journal-title":"Experimental gerontology","ISSN":"https:\/\/id.crossref.org\/issn\/0531-5565","issn-type":"print"},{"issue":"2","key":"13_13474859","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/BF01534707","volume":"11","author":"Riddell","year":"1985","journal-title":"Somatic cell and molecular genetics","ISSN":"https:\/\/id.crossref.org\/issn\/0740-7750","issn-type":"print"},{"issue":"13","key":"14_10757582","doi-asserted-by":"publisher","first-page":"9029","DOI":"10.1074\/jbc.274.13.9029","volume":"274","author":"Ito","year":"1999","journal-title":"Journal of Biological Chemistry","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9258","issn-type":"print"},{"issue":"11","key":"15_17943354","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1172\/JCI200318616","volume":"112","author":"Russell","year":"2003","journal-title":"Journal of Clinical Investigation","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9738","issn-type":"print"},{"issue":"19","key":"16_19567649","doi-asserted-by":"publisher","first-page":"19441","DOI":"10.1074\/jbc.M310249200","volume":"279","year":"2004","journal-title":"Journal of Biological Chemistry","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9258","issn-type":"print"},{"issue":"5","key":"17_17027486","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1530\/eje.0.1460649","volume":"146","author":"Rutishauser","year":"2002","journal-title":"European Journal of Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"},{"issue":"16","key":"18_22350336","doi-asserted-by":"publisher","first-page":"4000","DOI":"10.1016\/j.febslet.2006.06.036","volume":"580","author":"Hofmann","year":"2006","journal-title":"FEBS Letters","ISSN":"https:\/\/id.crossref.org\/issn\/1873-3468","issn-type":"print"},{"issue":"8","key":"19_18397373","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.2337\/diacare.27.8.2003","volume":"27","author":"Smith","year":"2004","journal-title":"Diabetes Care","ISSN":"https:\/\/id.crossref.org\/issn\/0149-5992","issn-type":"print"},{"issue":"4","key":"20_18128036","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1210\/jc.2002-030015","volume":"89","author":"Medlej","year":"2004","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"},{"issue":"8988","key":"21_16093236","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1016\/S0140-6736(95)92473-6","volume":"346","author":"Barrett","year":"1995","journal-title":"Lancet","ISSN":"https:\/\/id.crossref.org\/issn\/0140-6736","issn-type":"print"},{"issue":"22","key":"22_11402017","doi-asserted-by":"publisher","first-page":"2501","DOI":"10.1093\/hmg\/10.22.2501","volume":"10","author":"Bespalova","year":"2001","journal-title":"Human Molecular Genetics","ISSN":"https:\/\/id.crossref.org\/issn\/0964-6906","issn-type":"print"},{"issue":"6","key":"23_31290421","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1111\/j.1464-5491.2008.02448.x","volume":"25","author":"Valero","year":"2008","journal-title":"Diabetic medicine : a journal of the British Diabetic Association","ISSN":"https:\/\/id.crossref.org\/issn\/0742-3071","issn-type":"print"},{"key":"24_48844228","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1002\/ajmg.a.33970","volume":"155","year":"2011","journal-title":"American journal of medical genetics. Part A","ISSN":"https:\/\/id.crossref.org\/issn\/1552-4825","issn-type":"print"},{"key":"25_49919387","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1038\/ejhg.2013.52","volume":"21","year":"2013","journal-title":"European journal of human genetics : EJHG","ISSN":"https:\/\/id.crossref.org\/issn\/1018-4813","issn-type":"print"},{"issue":"8","key":"26_29331154","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1038\/ng2067","volume":"39","author":"Sandhu","year":"2007","journal-title":"Nature genetics","ISSN":"https:\/\/id.crossref.org\/issn\/1061-4036","issn-type":"print"},{"issue":"21","key":"27_32616509","doi-asserted-by":"publisher","first-page":"2220","DOI":"10.1056\/NEJMoa0801869","volume":"359","author":"Lyssenko","year":"2008","journal-title":"New England Journal of Medicine","ISSN":"https:\/\/id.crossref.org\/issn\/0028-4793","issn-type":"print"},{"issue":"11","key":"28_44146472","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1093\/aje\/kws176","volume":"176","year":"2012","journal-title":"American Journal of Epidemiology","ISSN":"https:\/\/id.crossref.org\/issn\/0002-9262","issn-type":"print"},{"issue":"1","key":"29_5908908","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/sj.mp.4000344","volume":"3","author":"Swift","year":"1998","journal-title":"Molecular psychiatry","ISSN":"https:\/\/id.crossref.org\/issn\/1359-4184","issn-type":"print"},{"issue":"5","key":"30_11035224","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1093\/hmg\/10.5.477","volume":"10","author":"Takeda","year":"2001","journal-title":"Human Molecular Genetics","ISSN":"https:\/\/id.crossref.org\/issn\/0964-6906","issn-type":"print"},{"issue":"52","key":"31_19565763","doi-asserted-by":"publisher","first-page":"52755","DOI":"10.1074\/jbc.M310331200","volume":"278","year":"2003","journal-title":"Journal of Biological Chemistry","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9258","issn-type":"print"},{"issue":"4","key":"32_17796805","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1002\/humu.10258","volume":"22","author":"Cryns","year":"2003","journal-title":"Human mutation","ISSN":"https:\/\/id.crossref.org\/issn\/1059-7794","issn-type":"print"},{"issue":"10","key":"33_21840041","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1093\/hmg\/ddl081","volume":"15","year":"2006","journal-title":"Human Molecular Genetics","ISSN":"https:\/\/id.crossref.org\/issn\/0964-6906","issn-type":"print"},{"issue":"47","key":"34_19602434","doi-asserted-by":"publisher","first-page":"39609","DOI":"10.1074\/jbc.M507426200","volume":"280","year":"2005","journal-title":"Journal of Biological Chemistry","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9258","issn-type":"print"},{"issue":"2","key":"35_6181390","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/2441","volume":"20","author":"Inoue","year":"1998","journal-title":"Nature genetics","ISSN":"https:\/\/id.crossref.org\/issn\/1061-4036","issn-type":"print"},{"issue":"5","key":"36_11124193","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1002\/humu.1110","volume":"17","author":"Khanim","year":"2001","journal-title":"Human mutation","ISSN":"https:\/\/id.crossref.org\/issn\/1059-7794","issn-type":"print"},{"issue":"4","key":"37_11106264","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/humu.32","volume":"17","author":"Tessa","year":"2001","journal-title":"Human mutation","ISSN":"https:\/\/id.crossref.org\/issn\/1059-7794","issn-type":"print"},{"key":"38_49919388","first-page":"1605","volume":"143","year":"2007","journal-title":"American journal of medical genetics","ISSN":"https:\/\/id.crossref.org\/issn\/0148-7299","issn-type":"print"},{"issue":"7","key":"39_19273413","doi-asserted-by":"crossref","first-page":"4388","DOI":"10.1210\/jc.2004-2000","volume":"90","year":"2005","journal-title":"Journal of Clinical Endocrinology &amp; Metabolism","ISSN":"https:\/\/id.crossref.org\/issn\/0021-972X","issn-type":"print"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/172\/4\/461.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/172\/4\/461.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:32:04Z","timestamp":1676392324000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/172\/4\/461\/6668034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4]]},"references-count":39,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.1530\/eje-14-0942","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4]]}}}