{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T12:04:34Z","timestamp":1792929874094,"version":"4.5.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Mutations in <jats:italic>AQP2 (aquaporin-2)<\/jats:italic> lead to rare congenital nephrogenic diabetes insipidus (NDI), which has been limitedly studied in Chinese population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty-five subjects from seven families with NDI in a department (Beijing, PUMCH) were screened for <jats:italic>AQP2<\/jats:italic> mutations. Clinical characteristics were described and genotype-phenotype correlation analysis was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 9 <jats:italic>AQP2<\/jats:italic> mutations in 13 patients with NDI, including 3 novel <jats:italic>AQP2<\/jats:italic> mutations (p.G165D, p.Q255RfsTer72 and IVS3-3delC). Missense mutations were the most common mutation type, followed by splicing mutations, and frameshift mutations caused by small deletion or insertion. The onset-age in our patients was younger than 1 year old. Common manifestations included polydipsia, polyuria (7\/7) and intermittent fever (6\/7). Less common presentations included short stature (3\/7) and mental impairment (1\/7). High osmotic hypernatremia and low osmotic urine were the main biochemical features. Dilation of the urinary tract was a common complication of NDI (3\/6). Level of serum sodium in NDI patients with compound het AQP2 mutations was higher than non-compound het mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In the first and largest case series of NDI caused by <jats:italic>AQP2<\/jats:italic> mutation in Chinese population, we identified 9 <jats:italic>AQP2<\/jats:italic> mutations, including 3 novel mutations. Phenotype was found to correlate with genotypes, revealed by higher level of serum sodium in patients with compound het <jats:italic>AQP2<\/jats:italic> mutations than non-compound het mutations. This knowledge broadens genotypic and phenotypic spectrum for rare congenital NDI and provided basis for studying molecular biology of AQP2.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2021.686818","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T14:34:11Z","timestamp":1623335651000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Novel AQP2 Mutations and Clinical Characteristics in Seven Chinese Families With Congenital Nephrogenic Diabetes Insipidus"],"prefix":"10.3389","volume":"12","author":[{"given":"Qian","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Cen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weibo","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2015.89","article-title":"Pathophysiology, Diagnosis and Management of Nephrogenic Diabetes Insipidus","volume":"11","author":"Bockenhauer","year":"2015","journal-title":"Nat Rev Nephrol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/361549a0","article-title":"Cloning and Expression of Apical Membrane Water Channel of Rat Kidney Collecting Tubule","volume":"361","author":"Fushimi K","year":"1993","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-012-0726-z","article-title":"Hereditary Nephrogenic Diabetes Insipidus in Japanese Patients: Analysis of 78 Families and Report of 22 New Mutations in AVPR2 and AQP2","volume":"17","author":"Sasaki. 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