{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T08:26:34Z","timestamp":1792052794776,"version":"4.4.0"},"reference-count":42,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2009,4,18]],"date-time":"2009-04-18T00:00:00Z","timestamp":1240012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2009,4,18]],"date-time":"2009-04-18T00:00:00Z","timestamp":1240012800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nephron Physiol"],"abstract":"<i>Background\/Aims:<\/i> Dent disease is an X-linked renal proximal tubulopathy associated with mutations in<i> CLCN5<\/i> (Dent 1) or<i> OCRL1<\/i> (Dent 2). <i>OCRL1<\/i> mutations also cause the oculocerebrorenal syndrome of Lowe. <i>Methods:<\/i> Dent patients with normal sequence for <i>CLCN5<\/i> were sequenced for mutations in <i>OCRL1<\/i>. By analyzing these and all other <i>OCRL1<\/i> mutations reported, a model relating <i>OCRL1<\/i> mutations to the resulting disease (Dent 2 or Lowe\u2019s) was developed. <i>Results:<\/i> Six boys with Dent disease had novel <i>OCRL1 <\/i>mutations: two missense (R301H, G304E) and four mutations predicted to produce premature termination codons (L56DfsX1, S149X, P161PfsX3, and M170IfsX1). These include one of the original patients reported by Dent and Friedman. Slit lamp examinations revealed early cataracts in only one boy with normal vision. None of these Dent 2 patients had metabolic acidosis; 3 had mild mental retardation. Analysis of all known <i>OCRL1<\/i> mutations show that Dent 2 mutations fall into two classes that do not overlap with Lowe mutations. Bioinformatics analyses identified expressed <i>OCRL1<\/i> splice variants that help explain the variability of those clinical features that distinguish Dent disease from Lowe syndrome. <i>Conclusions:<\/i><i>OCRL1<\/i> mutations can cause the renal phenotype of Dent disease, without acidosis or the dramatic eye abnormalities typical of Lowe syndrome. We propose a model to explain the phenotypic variability between Dent 2 and Lowe\u2019s based on distinctly different classes of mutations in <i>OCRL1<\/i> producing splice variants.<\/jats:p>","DOI":"10.1159\/000213506","type":"journal-article","created":{"date-parts":[[2009,4,20]],"date-time":"2009-04-20T15:36:39Z","timestamp":1240241799000},"page":"p27-p36","source":"Crossref","is-referenced-by-count":87,"title":["<i>OCRL1<\/i> Mutations in Dent 2 Patients Suggest a Mechanism for Phenotypic Variability"],"prefix":"10.1159","volume":"112","author":[{"given":"Antony E.","family":"Shrimpton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard R.","family":"Hoopes, Jr.","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen 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