{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:37:16Z","timestamp":1790271436304,"version":"4.1.0"},"reference-count":11,"publisher":"American Diabetes Association","issue":"9","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,9,1]]},"abstract":"<jats:p>OBJECTIVE\u2014Wolfram syndrome is an autosomal recessive neurodegenerative disorder characterized by diabetes insipidus, diabetes (nonautoimmune), optic atrophy, and deafness (a set of conditions referred to as DIDMOAD). The WFS1 gene is located on the short arm of chromosome 4. Wolfram syndrome prevalence is 1 in 770,000 live births, with a 1 in 354 carrier frequency.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014We evaluated six Italian children from five unrelated families. Genetic analysis for Wolfram syndrome was performed by PCR amplification and direct sequencing.<\/jats:p>\n               <jats:p>RESULTS\u2014Mutation screening revealed five distinct variants, one novel mutation (c.1346C&amp;gt;T; p.T449I) and four previously described, all located in exon 8.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014Phenotype-genotype correlation is difficult, and the same mutation gives very different phenotypes. Severely inactivating mutations result in a more severe phenotype than mildly inactivating ones. Clinical follow-up showed the progressive syndrome's seriousness.<\/jats:p>","DOI":"10.2337\/dc08-0178","type":"journal-article","created":{"date-parts":[[2008,6,20]],"date-time":"2008-06-20T01:51:02Z","timestamp":1213926662000},"page":"1743-1745","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":39,"title":["Wolfram Syndrome (Diabetes Insipidus, Diabetes, Optic Atrophy, and Deafness)"],"prefix":"10.2337","volume":"31","author":[{"given":"Giuseppe","family":"d'Annunzio","sequence":"first","affiliation":[{"name":"Pediatric Clinic, University of Genoa, G. Gaslini Institute, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Minuto","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, University of Genoa, G. Gaslini Institute, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"D'Amato","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, University of Genoa, G. Gaslini Institute, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"de Toni","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, University of Genoa, G. Gaslini Institute, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fortunato","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Sciences, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Pasquali","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, University of Genoa, G. Gaslini Institute, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Lorini","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, University of Genoa, G. Gaslini Institute, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031218503068300_R1","doi-asserted-by":"crossref","unstructured":"Barrett TG, Bundey SE, Macleod AF: Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet\u2008346:1458\u20131463, 1995","DOI":"10.1016\/S0140-6736(95)92473-6"},{"key":"2022031218503068300_R2","doi-asserted-by":"crossref","unstructured":"Medlej R, Wasson J, Baz P, Azar S, Salti I, Loiselet J, Permutt A, Halaby G: Diabetes mellitus and optic atrophy: a study of Wolfram syndrome in the Lebanese population. J Clin Endocrinol Metab\u200889:1656\u20131661, 2004","DOI":"10.1210\/jc.2002-030015"},{"key":"2022031218503068300_R3","doi-asserted-by":"crossref","unstructured":"Inoue H, Tanizawa Y, Wasson J, Behn P, Kalidas K, Bernal-Mizrachi E, Mueckler M, Marshall H, Donis-Keller H, Crock P, Rogers D, Mikuni M, Kumashiro H, Higashi K, Sobue G, Oka Y, Permutt MA: A gene encoding a transmembrane protein in mutated patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nat Genet\u200820:143\u2013148, 1998","DOI":"10.1038\/2441"},{"key":"2022031218503068300_R4","doi-asserted-by":"crossref","unstructured":"Riggs AC, Bernal-Mizrachi E, Ohsugi M, Wasson J, Fatrai S, Welling C, Murray J, Schmidt RE, Herrera PL, Permutt MA: Mice conditionally lacking the Wolfram gene in pancreatic islet beta cells exhibit diabetes as a result of enhanced endoplasmic reticulum stress and apoptosis. Diabetologia\u200848:2313\u20132321, 2005","DOI":"10.1007\/s00125-005-1947-4"},{"key":"2022031218503068300_R5","doi-asserted-by":"crossref","unstructured":"Pakdemirli E, Karabulut N, Bir LS, Sermez Y: Cranial magnetic resonance imaging of Wolfram (DIDMOAD) syndrome. Australas Radiol\u200849:189\u2013191, 2005","DOI":"10.1111\/j.1440-1673.2005.01420.x"},{"key":"2022031218503068300_R6","doi-asserted-by":"crossref","unstructured":"Piccoli GB, Mezza E, Jeantet A, Segoloni JP: An uncommon genetic syndrome with acute renal failure in a 30-year-old diabetic patient. Nephrol Dial Transplant\u200818:206\u2013208, 2003","DOI":"10.1093\/ndt\/18.1.206"},{"key":"2022031218503068300_R7","doi-asserted-by":"crossref","unstructured":"Colosimo A, Guida V, Rigoli L, Di Bella C, De Luca A, Briuglia S, Stuppia L, Salpietro DC, Dallapiccola B: Molecular detection of novel WFS1 mutations in patients with Wolfram syndrome by a DHPLC-based assay. Hum Mutat\u200821:622\u2013629, 2003","DOI":"10.1002\/humu.10215"},{"key":"2022031218503068300_R8","doi-asserted-by":"crossref","unstructured":"Tessa A, Carbone I, Matteoli MC, Bruno C, Patrono C, Patera IP, De Luca F, Lorini R, Santorelli FM: Identification of Novel WFS1 Mutations in Italian Children With Wolfram Syndrome. Hum Mutat\u20087:348\u2013349, 2001","DOI":"10.1002\/humu.32"},{"key":"2022031218503068300_R9","doi-asserted-by":"crossref","unstructured":"Smith CJ, Crock PA, King BR, Meldrum CJ, Scott RJ: Phenotype-genotype correlations in a series of Wolfram syndrome families. Diabetes Care\u200827:2003\u20132009, 2004","DOI":"10.2337\/diacare.27.8.2003"},{"key":"2022031218503068300_R10","unstructured":"Fabbri LP, Nucera M, Grippo A, Menicucci A, De Feo ML, Becchi C, Al Malyan M: Wolfram syndrome: how much could knowledge challenge the fate? A case report. Med Sci Monit\u200811:CS40\u2013CS44, 2005"},{"key":"2022031218503068300_R11","doi-asserted-by":"crossref","unstructured":"Philbrook C, Fritz E, Weiher H: Expressional and functional studies of Wolframin, the gene function deficient in Wolfram syndrome, in mice and patient cells. Exper Gerontol\u200840:671\u2013678, 2005","DOI":"10.1016\/j.exger.2005.06.008"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/31\/9\/1743\/599599\/zdc00908001743.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/31\/9\/1743\/599599\/zdc00908001743.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T19:58:40Z","timestamp":1647115120000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/31\/9\/1743\/27891\/Wolfram-Syndrome-Diabetes-Insipidus-Diabetes-Optic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,9,1]]},"references-count":11,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2008,9,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc08-0178","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,9,1]]}}}