{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:50:27Z","timestamp":1792590627079,"version":"4.5.0"},"reference-count":18,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2005,3,24]],"date-time":"2005-03-24T00:00:00Z","timestamp":1111622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2005,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Objectives<\/jats:bold> Multisystem pseudohypoaldosteronism (PHA) is a rare autosomal recessive aldosterone unresponsiveness syndrome that results from mutations in the genes encoding epithelial sodium channel (ENaC) subunits \u03b1, \u03b2 and \u03b3. In this study we examined three PHA patients to identify mutations responsible for PHA with different clinical presentations.<\/jats:p><jats:p><jats:bold>Patients<\/jats:bold> All three patients presented uniformly with symptoms of severe salt\u2010loss during the first week of life and were hospitalized for up to a year. Beyond infancy, one of the patients showed mild renal salt loss and had no lower respiratory tract infections until 8\u00a0years of age, while the other patients continue with a severe course.<\/jats:p><jats:p><jats:bold>Results<\/jats:bold> We sequenced the complete coding regions and intron\u2013exon junctions of the genes encoding \u03b1, \u03b2 and \u03b3 subunits of ENaC for all patients. The results revealed that the mild case represents a novel compound heterozygote including a missense (Gly327Cys) mutation in the \u03b1ENaC gene. Sequences of relatives over three generations confirmed that the missense mutation co\u2010segregates with PHA. This mutation was not found in 60 control subjects. The other patients with severe PHA had two homozygous mutations, a novel deletion mutation in exon\u00a08 of the \u03b1ENaC gene and a splice site mutation in intron\u00a012 of the \u03b2ENaC gene. Most of the PHA\u2010causing mutations appear in the \u03b1ENaC gene located on chromosome\u00a012 rather than in the \u03b2 and \u03b3ENaC genes located tandemly on chromosome\u00a016. However, the frequency of sequence variants in patients and control subjects showed no difference between genes.<\/jats:p><jats:p><jats:bold>Conclusions<\/jats:bold> Severe PHA cases are associated with mutations leading to absence of normal\u2010length \u03b1, \u03b2 or \u03b3ENaC, while a mild case has been found to be associated with a missense mutation in \u03b1ENaC. The predominance of PHA\u2010causing mutations in the \u03b1ENaC gene may be related to the function of this subunit.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2005.02255.x","type":"journal-article","created":{"date-parts":[[2005,4,21]],"date-time":"2005-04-21T10:09:33Z","timestamp":1114078173000},"page":"547-553","source":"Crossref","is-referenced-by-count":72,"title":["Novel mutations in epithelial sodium channel (ENaC) subunit genes and phenotypic expression of multisystem pseudohypoaldosteronism"],"prefix":"10.1111","volume":"62","author":[{"given":"Oded","family":"Edelheit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel","family":"Hanukoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gizewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurgun","family":"Kandemir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yardena","family":"Tenenbaum\u2010Rakover","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Yurdak\u00f6k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanislaw","family":"Zajaczek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Hanukoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,3,24]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-73-5-936"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2004.06.003"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.12.4690"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0396-248"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0696-248"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.2.293"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199907153410304"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(99)70094-6"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.1.9"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-002-0945-8"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.87.7.3344"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/367463a0"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9625"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.64.082101.143243"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1997.77.2.359"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-48-2-228"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(06)80176-9"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2002-0029OC"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2265.2005.02255.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2265.2005.02255.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T09:02:50Z","timestamp":1697187770000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2265.2005.02255.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3,24]]},"references-count":18,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2005,5]]}},"alternative-id":["10.1111\/j.1365-2265.2005.02255.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2265.2005.02255.x","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,3,24]]}}}