{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T07:50:15Z","timestamp":1753861815451,"version":"3.41.2"},"reference-count":17,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Loss\u2010of\u2010function mutations of <jats:italic>AVPR2<\/jats:italic> and <jats:italic>L1CAM<\/jats:italic> result in nephrogenic diabetes insipidus (NDI) and L1 syndrome. These diseases are inherited in an X\u2010linked recessive manner. Females with heterozygous variants can be affected owing to skewed X\u2010chromosome inactivation (XCI). A 3\u2010year\u2010old girl with normal development was presented with polydipsia and polyuria, and diagnosed of NDI through an improper response to water restriction and desmopressin administration. A targeted genome capture sequencing for X chromosome confirmed Xq28 microdeletion involving <jats:italic>AVPR2<\/jats:italic> and <jats:italic>L1CAM<\/jats:italic>, derived from mother with mosaicism of the deletion. No pathogenic variants were identified in the paternal X allele nor in <jats:italic>AQP2<\/jats:italic>, another causative gene of NDI. XCI was exclusively skewed toward the maternal X chromosome in hair, oral mucosa, and blood, while it was random in nails and renal tubular epithelial cells (RTECs). Both <jats:italic>AVPR2<\/jats:italic> and <jats:italic>L1CAM<\/jats:italic> mRNA expression in the patient's RTECs were significantly reduced compared to those of controls, with <jats:italic>AVPR2<\/jats:italic> showing a more pronounced decrease. Thus, we demonstrated for the first time that NDI can develop in a female with a <jats:italic>AVPR2<\/jats:italic> deletion despite of random XCI. Moreover, the absence of L1 syndrome in the female patient was caused most probably through organ\u2010dependent skewed XCI in the deletion allele.<\/jats:p>","DOI":"10.1002\/ajmg.a.64024","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T20:51:11Z","timestamp":1741726271000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and Molecular Genetic Analyses of a Girl With Isolated Nephrogenic Diabetes Insipidus due to Contiguous Gene Deletion Involving <i>AVPR2<\/i> and <i>L1CAM<\/i>"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2312-1094","authenticated-orcid":false,"given":"Shoma","family":"Saito","sequence":"first","affiliation":[{"name":"Department of Pediatrics Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeru","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kengo","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takumi","family":"Kamiyama","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kosuke","family":"Saito","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hinako","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahide","family":"Kokumai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko","family":"Furuya","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genya","family":"Taketazu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Asahikawa Kosei General Hospital  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshio","family":"Makita","sequence":"additional","affiliation":[{"name":"Department of Genetic Counseling Asahikawa Medical University Hospital  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5641-7962","authenticated-orcid":false,"given":"Yo","family":"Niida","sequence":"additional","affiliation":[{"name":"Center for Clinical Genomics Kanazawa Medical University Hospital  Uchinada Japan"},{"name":"Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute Kanazawa Medical University  Uchinada Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4707-4010","authenticated-orcid":false,"given":"Satoru","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Asahikawa Medical University  Asahikawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Bichet D. 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