{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T17:24:04Z","timestamp":1775841844580,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T00:00:00Z","timestamp":1582070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>There are two forms of diabetes insipidus, central (neurohypophyseal), and nephrogenic, caused by pathogenic variants in the <jats:italic>AVP<\/jats:italic> gene and the <jats:italic>AVPR2<\/jats:italic> or <jats:italic>AQP2<\/jats:italic> genes, respectively. We report on a four\u2010generation family, seven individuals had central diabetes insipidus (CDI) and the female index patient seen from age 16 to 26\u2009years had (mild) nephrogenic diabetes insipidus. In her father with CDI, a known pathogenic heterozygous <jats:italic>AVP<\/jats:italic> variant c.232_234del p.(Glu78del) was identified, confirming the diagnosis of CDI in him and the other affected family members. In the proband, molecular analysis disclosed a novel heterozygous <jats:italic>AVPR2<\/jats:italic> gene variant, c.962A\u2009&gt;\u2009T p.(Asn321Ile) and an extremely skewed X\u2010inactivation, confirming X\u2010linked nephrogenic diabetes insipidus (XL\u2010NDI). Whole exome sequencing showed no further causative mutation. This is the first report on the co\u2010existence of CDI and NDI in one family. Our review of symptomatic female <jats:italic>AVPR2<\/jats:italic> heterozygotes includes 23 families with at least one affected female (including this study). There were 21 different causative mutations. Mutation types in females did not differ from those in males. Both severe XL\u2010NDI and mild forms were reported in females. All six females with severe XL\u2010NDI had complete loss\u2010of\u2010function (null) mutations. The remaining 17 female probands had milder XL\u2010NDI caused by 14 missense variants and three null variants of the <jats:italic>AVPR2<\/jats:italic> gene. X\u2010inactivation was studied in nine of these females; all showed extreme or slight skewing. The review underlines that XL\u2010NDI in female <jats:italic>AVPR2<\/jats:italic> heterozygotes is always accompanied by skewed X\u2010inactivation, emphasizing a need for X\u2010inactivation studies in these females.<\/jats:p>","DOI":"10.1002\/ajmg.a.61516","type":"journal-article","created":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T13:20:43Z","timestamp":1582118443000},"page":"1032-1040","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A female with X\u2010linked Nephrogenic diabetes insipidus in a family with inherited central diabetes Insipidus: Case report and review of the literature"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1561-2953","authenticated-orcid":false,"given":"Can","family":"Ding","sequence":"first","affiliation":[{"name":"Institute of Human Genetics University Medical Centre of the Johannes Gutenberg University  Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf","family":"Beetz","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Unit of the Children's Hospital University Medical Centre of the Johannes Gutenberg University  Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Rittner","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Centre of the Johannes Gutenberg University  Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Bartsch","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Centre of the Johannes Gutenberg University  Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,2,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1681\/ASN.V9101861","article-title":"Functional studies of twelve mutant V2 vasopressin receptors related to nephrogenic diabetes insipidus: Molecular basis of a mild clinical phenotype","volume":"9","author":"Ala Y.","year":"1998","journal-title":"Journal of the American Society of Nephrology"},{"key":"e_1_2_9_3_1","first-page":"1229","article-title":"Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen\u2010receptor gene correlates with X chromosome inactivation","volume":"51","author":"Allen R. 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