{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T20:52:04Z","timestamp":1761511924005},"reference-count":19,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a defect in free water conservation caused by mutations in the single gene that encodes both vasopressin (VP) and its binding protein, neurophysin II (NP II). Most of the human mutations in this gene have been in the portion encoding the NP molecule; the resultant abnormal gene products are believed to cause cellular toxicity as improperly folded precursor molecules accumulate in the endoplasmic reticulum. We identified a new American kindred with ADNDI and found a novel mutation in the VP molecule. A 78-yr-old man was noted to have hypotonic polyuria and plasma hyperosmolarity; the urinary concentration defect was reversed by administration of VP. His symptomatology dated to childhood, and his family history was consistent with autosomal transmission of the polyuric syndrome, with affected members in three generations, including several females. Affected individuals were found to be heterozygous for a 3-bp deletion in exon 1 of arginine VP (AVP)-NP II, predicting a deletion of phenylalanine 3 (known to be critical for receptor binding) in the VP nonapeptide. Neuro 2A cells stably transfected with the mutant AVP-NP construct showed increased rates of apoptosis as assessed by flow cytometric methods. These observations support the concept that cellular toxicity of abnormal AVP-NP gene products underlies the development of ADNDI, and the data further demonstrate that mutations affecting the AVP moiety can result in initiation of these pathological processes.<\/jats:p>","DOI":"10.1210\/jc.2003-031542","type":"journal-article","created":{"date-parts":[[2004,4,7]],"date-time":"2004-04-07T22:23:39Z","timestamp":1081376619000},"page":"1963-1968","source":"Crossref","is-referenced-by-count":20,"title":["A Novel Mutation in the Preprovasopressin Gene Identified in a Kindred with Autosomal Dominant Neurohypophyseal Diabetes Insipidus"],"prefix":"10.1210","volume":"89","author":[{"given":"Justin T.","family":"Wahlstrom","sequence":"first","affiliation":[{"name":"Division of Diabetes, Endocrinology, and Metabolism (J.T.W., M.J.F., W.E.N., W.J.K.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Fowler","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Endocrinology, and Metabolism (J.T.W., M.J.F., W.E.N., W.J.K.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendell E.","family":"Nicholson","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Endocrinology, and Metabolism (J.T.W., M.J.F., W.E.N., W.J.K.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J.","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Endocrinology, and Metabolism (J.T.W., M.J.F., W.E.N., W.J.K.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232"},{"name":"United States Department of Veterans Affairs (W.J.K.), Tennessee Valley Healthcare System, Nashville, Tennessee 37212"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071616442157600_R1","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1210\/jcem.87.7.8677","article-title":"Autosomal dominant neurohypophyseal diabetes insipidus due to substitution of histidine for tyrosine(2) in the vasopressin moiety of the hormone precursor.","volume":"87","author":"Rittig","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616442157600_R2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1023\/A:1022564803093","article-title":"Structure-function relationships of the vasopressin prohormone domains.","volume":"18","author":"De Bree","year":"1998","journal-title":"Cell Mol Neurobiol"},{"key":"2020071616442157600_R3","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1046\/j.1365-2826.2000.00521.x","article-title":"Trafficking of the vasopressin and oxytocin prohormone through the regulated secretory pathway.","volume":"12","author":"De Bree","year":"2000","journal-title":"J Neuroendocrinol"},{"key":"2020071616442157600_R4","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0014-5793(00)01623-9","article-title":"Sorting of the vasopressin prohormone into the regulated secretory pathway.","volume":"475","author":"De Bree","year":"2000","journal-title":"FEBS Lett"},{"key":"2020071616442157600_R5","first-page":"3410","article-title":"Familial neurohypophysial diabetes insipidus in a large Dutch kindred: effect of the onset of diabetes on growth in children and cell biological defects of the mutant vasopressin prohormone.","volume":"86","author":"Nijenhuis","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616442157600_R6","doi-asserted-by":"crossref","first-page":"9029","DOI":"10.1074\/jbc.274.13.9029","article-title":"Mutant vasopressin precursors that cause autosomal dominant neurohypophyseal diabetes insipidus retain dimerization and impair the secretion of wild-type proteins.","volume":"274","author":"Ito","year":"1999","journal-title":"J Biol Chem"},{"key":"2020071616442157600_R7","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1172\/JCI119357","article-title":"Molecular basis of autosomal dominant neurohypophyseal diabetes insipidus. Cellular toxicity caused by the accumulation of mutant vasopressin precursors within the endoplasmic reticulum.","volume":"99","author":"Ito","year":"1997","journal-title":"J Clin Invest"},{"key":"2020071616442157600_R8","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1089\/dna.1996.15.929","article-title":"Heterologous expression of human vasopressin-neurophysin precursors in a pituitary cell line: defective transport of a mutant protein from patients with familial diabetes insipidus.","volume":"15","author":"Olias","year":"1996","journal-title":"DNA Cell Biol"},{"key":"2020071616442157600_R9","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0303-7207(00)00288-4","article-title":"A diabetes insipidus vasopressin prohormone altered outside the central core of neurophysin accumulates in the endoplasmic reticulum.","volume":"167","author":"Nijenhuis","year":"2000","journal-title":"Mol Cell Endocrinol"},{"key":"2020071616442157600_R10","first-page":"2933","article-title":"Clinical and molecular evidence of abnormal processing and trafficking of the vasopressin preprohormone in a large kindred with familial neurohypophyseal diabetes insipidus due to a signal peptide mutation.","volume":"84","author":"Siggaard","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616442157600_R11","doi-asserted-by":"crossref","first-page":"18965","DOI":"10.1074\/jbc.274.27.18965","article-title":"Mechanism of endoplasmic reticulum retention of mutant vasopressin precursor caused by a signal peptide truncation associated with diabetes insipidus.","volume":"274","author":"Beuret","year":"1999","journal-title":"J Biol Chem"},{"key":"2020071616442157600_R12","doi-asserted-by":"crossref","first-page":"4240","DOI":"10.1073\/pnas.88.10.4240","article-title":"Crystal structure of a bovine neurophysin II dipeptide complex at 2.8 A determined from the single-wavelength anomalous scattering signal of an incorporated iodine atom.","volume":"88","author":"Chen","year":"1991","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071616442157600_R13","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1172\/JCI115052","article-title":"A single base substitution in the coding region for neurophysin II associated with familial central diabetes insipidus.","volume":"87","author":"Ito","year":"1991","journal-title":"J Clin Invest"},{"key":"2020071616442157600_R14","first-page":"1787","article-title":"A new type of familial central diabetes insipidus caused by a single base substitution in the neurophysin II coding region of the vasopressin gene.","volume":"81","author":"Ueta","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616442157600_R15","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1093\/hmg\/8.7.1303","article-title":"Autosomal recessive familial neurohypophyseal diabetes insipidus with continued secretion of mutant weakly active vasopressin.","volume":"8","author":"Willcutts","year":"1999","journal-title":"Hum Mol Genet"},{"key":"2020071616442157600_R16","first-page":"870","article-title":"Effects of aging on vasopressin production in a kindred with autosomal dominant neurohypophyseal diabetes insipidus due to the \u0394E47 neurophysin mutation.","volume":"87","author":"Mahoney","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616442157600_R17","first-page":"3643","article-title":"Autosomal dominant neurohypophyseal diabetes insipidus associated with a missense mutation encoding Gly23\u2192Val in neurophysin II.","volume":"82","author":"Gagliardi","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616442157600_R18","first-page":"51","article-title":"Heterogeneity in clinical manifestation of autosomal dominant neurohypophyseal diabetes insipidus caused by a mutation encoding Ala-1\u2192Val in the signal peptide of the arginine vasopressin\/neurophysin II\/copeptin precursor.","volume":"82","author":"Repaske","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616442157600_R19","first-page":"192","article-title":"A novel point mutation in the translation initiation codon of the pre-pro-vasopressin-neurophysin II gene: cosegregation with morphological abnormalities and clinical symptoms in autosomal dominant neurohypophyseal diabetes insipidus.","volume":"81","author":"Rutishauser","year":"1996","journal-title":"J Clin Endocrinol Metab"}],"container-title":["The Journal of Clinical Endocrinology &amp; 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