{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:35:33Z","timestamp":1790264133475,"version":"4.1.0"},"reference-count":28,"publisher":"American Academy of Pediatrics (AAP)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,3,1]]},"abstract":"<jats:sec>\n                  <jats:title>Objective.<\/jats:title>\n                  <jats:p>To ascertain the clinical scenarios in which genetic testing for congenital nephrogenic diabetes insipidus (NDI) by direct detection of mutations might prove valuable, and to assess the use of automated sequencing for testing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods.<\/jats:title>\n                  <jats:p>We reviewed NDI cases referred to our research laboratory for enrollment in our study of mutations in the AVPR2 gene that is disrupted in the X-linked form of the disease. We selected 5 cases that illustrate the value of genetic testing in different clinical situations. Clinical information was obtained from the patient's personal physicians and the patients' families. Direct automated fluorescent DNA sequencing of AVPR2 gene amplification product was used to identify disease-associated mutations in patients. The presence or absence of mutations in family members was then established by using automated sequencing, restriction enzyme analysis, or both.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results.<\/jats:title>\n                  <jats:p>In 2 of the 5 selected cases, the diagnosis of a genetic form of NDI was confirmed by mutation analysis in a sporadic case of an affected boy. In 2 cases, a suspected diagnosis of X-linked NDI was confirmed in an affected girl. In 4 of the cases, 1 or more unaffected female relatives were determined to carry or not to carry the disease-associated gene. In 2 cases, testing of the newborn child of a known or suspected carrier confirmed the clinical suspicion of affected status and justified proactive therapy. In 4 of the 5 cases, the mode of inheritance was not clear from the family history and was established as X-linked by the testing. Assay for restriction sites changed by disease-associated mutations agreed with the automated sequencing results.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions.<\/jats:title>\n                  <jats:p>We conclude that direct mutation analysis in patients suspected of NDI and in selected family members is indicated. The results of testing can confirm a clinical diagnosis of disease, which may otherwise be difficult to make in girls. It can further establish the mode of inheritance, unambiguously distinguish carriers from noncarriers, and justify special observation or treatment of newborns at risk, thereby averting dehydration and the attendant complications. We also conclude that, with proper controls, automated sequencing is the preferred method of testing, because it is sufficiently robust, sensitive, and adaptable for this short gene with a large variety of causative mutations.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1542\/peds.103.3.632","type":"journal-article","created":{"date-parts":[[2004,8,13]],"date-time":"2004-08-13T23:45:45Z","timestamp":1092440745000},"page":"632-639","source":"Crossref","is-referenced-by-count":8,"title":["Clinical Utility of Direct Mutation Testing for Congenital Nephrogenic Diabetes Insipidus in Families"],"prefix":"10.1542","volume":"103","author":[{"given":"Robert S.","family":"Wildin","sequence":"first","affiliation":[{"name":"1 From the Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland, Oregon."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Cogdell","sequence":"additional","affiliation":[{"name":"1 From the Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland, Oregon."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[1999,3,1]]},"reference":[{"key":"2021121000390043600_B1"},{"key":"2021121000390043600_B2","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1046\/j.1523-1755.1998.00214.x","article-title":"AVPR2 variants and V2 vasopressin receptor function in nephrogenic diabetes insipidus.","volume":"54","author":"Wildin","year":"1998","journal-title":"Kidney Int."},{"key":"2021121000390043600_B3","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/BF00214189","article-title":"Clinical phenotype of nephrogenic diabetes insipidus in females heterozygous for a vasopressin type 2 receptor mutation.","volume":"96","author":"van Lieburg","year":"1995","journal-title":"Hum Genet."},{"key":"2021121000390043600_B4","doi-asserted-by":"crossref","first-page":"3434","DOI":"10.1210\/jcem.82.10.4312","article-title":"Detection of skewed X-inactivation in two female carriers of vasopressin type 2 receptor gene mutation.","volume":"82","author":"Nomura","year":"1997","journal-title":"J Clin Endocrinol Metab."},{"key":"2021121000390043600_B5","first-page":"648","article-title":"Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene.","volume":"55","author":"van Lieburg","year":"1994","journal-title":"Am J Hum Genet."},{"key":"2021121000390043600_B6"},{"key":"2021121000390043600_B7","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1093\/hmg\/3.9.1685","article-title":"Mutations in the vasopressin V2-receptor gene in three families of Italian descent with nephrogenic diabetes insipidus.","volume":"3","author":"Faa","year":"1994","journal-title":"Hum Mol 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Endocrinol."},{"key":"2021121000390043600_B15","first-page":"820","article-title":"Vasopressin V2 receptor mutants that cause X-linked nephrogenic diabetes insipidus: analysis of expression, processing, and function.","volume":"50","author":"Oksche","year":"1996","journal-title":"Mol Pharmacol."},{"key":"2021121000390043600_B16","doi-asserted-by":"crossref","first-page":"13030","DOI":"10.1016\/S0021-9258(19)38614-4","article-title":"Nephrogenic diabetes insipidus. A V2 vasopressin receptor unable to stimulate adenylyl cyclase.","volume":"268","author":"Rosenthal","year":"1993","journal-title":"J Biol Chem."},{"key":"2021121000390043600_B17","first-page":"429","article-title":"Mutations in the vasopressin V2 receptor gene in families with nephrogenic diabetes insipidus and functional expression of the Q-2 mutant.","volume":"40","author":"Rosenthal","year":"1994","journal-title":"Cell Mol Biol."},{"key":"2021121000390043600_B18","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1006\/bbrc.1995.1906","article-title":"Two vasopressin type 2 receptor gene mutations R143P and delta V278 in patients with nephrogenic diabetes insipidus impair ligand binding of the receptor.","volume":"211","author":"Tsukaguchi","year":"1995","journal-title":"Biochem Biophys Res Commun."},{"key":"2021121000390043600_B19","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/ki.1995.327","article-title":"Expression studies of two vasopressin V2 receptor gene mutations, R202C and 804insG, in nephrogenic diabetes insipidus.","volume":"48","author":"Tsukaguchi","year":"1995","journal-title":"Kidney Int."},{"key":"2021121000390043600_B20","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0303-7207(96)03926-3","article-title":"Functional characterization of five V2 vasopressin receptor gene mutations.","volume":"124","author":"Wenkert","year":"1996","journal-title":"Mol Cell Endocrinol."},{"key":"2021121000390043600_B21","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1681\/ASN.V73410","article-title":"A low-affinity vasopressin V2-receptor gene in a kindred with X-linked nephrogenic diabetes insipidus.","volume":"7","author":"Yokoyama","year":"1996","journal-title":"J Am Soc Nephrol."},{"key":"2021121000390043600_B22","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/ng1092-103","article-title":"Mutations in the V2 vasopressin receptor gene are associated with X-linked nephrogenic diabetes insipidus.","volume":"2","author":"Pan","year":"1992","journal-title":"Nat Genet."},{"key":"2021121000390043600_B23","doi-asserted-by":"crossref","first-page":"31933","DOI":"10.1016\/S0021-9258(18)31785-X","article-title":"The effect of eight V2 vasopressin receptor mutations on stimulation of adenylyl cyclase and binding to vasopressin.","volume":"269","author":"Pan","year":"1994","journal-title":"J Biol Chem."},{"key":"2021121000390043600_B24","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1093\/hmg\/6.11.1865","article-title":"Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response.","volume":"6","author":"Canfield","year":"1997","journal-title":"Hum Mol Genet."},{"key":"2021121000390043600_B25","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1126\/science.8140421","article-title":"Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine.","volume":"264","author":"Deen","year":"1994","journal-title":"Science."},{"key":"2021121000390043600_B26","first-page":"686","article-title":"Autosomal recessive nephrogenic diabetes insipidus caused by an aquaporin-2 mutation.","volume":"82","author":"Hochberg","year":"1997","journal-title":"J Clin Endocrinol Metab."},{"key":"2021121000390043600_B27","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s004390050264","article-title":"Two novel mutations in the aquaporin-2 and the vasopressin V2 receptor genes in patients with congenital nephrogenic diabetes insipidus.","volume":"98","author":"Oksche","year":"1996","journal-title":"Hum Genet."},{"key":"2021121000390043600_B28","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1681\/ASN.V8121855","article-title":"Mutations in the vasopressin V2 receptor and aquaporin-2 genes in 12 families with congenital nephrogenic diabetes 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