{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:04:34Z","timestamp":1791497074036,"version":"4.3.4"},"reference-count":24,"publisher":"American Diabetes Association","issue":"1","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,1,1]]},"abstract":"<jats:p>OBJECTIVE\u2014Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is caused by FOXP3 mutations. We aimed to determine the prevalence, genetics, and clinical phenotype of FOXP3 mutations in a large cohort with permanent neonatal diabetes (PNDM).<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014The 11 coding exons and the polyadenylation region of FOXP3 were sequenced in 26 male subjects with diabetes diagnosed before 6 months of age in whom common genetic causes of PNDM had been excluded. Ten subjects had at least one additional immune-related disorder, and the remaining 16 had isolated diabetes.<\/jats:p>\n               <jats:p>RESULTS\u2014We identified four hemizygous FOXP3 mutations in 6 of 10 patients with associated immune-related disorders and in 0 of 16 patients with isolated diabetes (P = 0.002). Three patients with two novel mutations (R337Q and P339A) and the previously reported L76QfsX53 developed classic IPEX syndrome and died within the first 13 months. The novel mutation V408M was found in three patients from two unrelated families and had a mild phenotype with hypothyroidism and autoimmune enteropathy (n = 2) or nephrotic syndrome (n = 1) and survival to 12\u201315 years.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014FOXP3 mutations result in \u223c4% of cases of male patients with permanent diabetes diagnosed before 6 months. Patients not only have classic IPEX syndrome but, unexpectedly, may have a more benign phenotype. FOXP3 sequencing should be performed in any male patient with the diagnosis of diabetes in the first 6 months who develops other possible autoimmune-associated conditions, even in the absence of full IPEX syndrome.<\/jats:p>","DOI":"10.2337\/dc08-1188","type":"journal-article","created":{"date-parts":[[2008,10,18]],"date-time":"2008-10-18T00:59:31Z","timestamp":1224291571000},"page":"111-116","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":106,"title":["Clinical Heterogeneity in Patients With <i>FOXP3<\/i> Mutations Presenting With Permanent Neonatal Diabetes"],"prefix":"10.2337","volume":"32","author":[{"given":"Oscar","family":"Rubio-Cabezas","sequence":"first","affiliation":[{"name":"Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, U.K."},{"name":"Department of Endocrinology, Hospital Infantil Universitario Nin\u0303o Jesus, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayne A.L.","family":"Minton","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Caswell","sequence":"additional","affiliation":[{"name":"School of Biosciences, Cardiff University, Cardiff, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian P.","family":"Shield","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Bristol Royal Hospital for Children, Bristol, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothee","family":"Deiss","sequence":"additional","affiliation":[{"name":"Department of Pediatric Diabetology and Endocrinology, Charite Campus, Virchow Childrens Hospital, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zdenek","family":"Sumnik","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amely","family":"Cayssials","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital Italiano de Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Herr","sequence":"additional","affiliation":[{"name":"Department of Pediatric Diabetology and Endocrinology, Charite Campus, Virchow Childrens Hospital, Berlin, Germany"},{"name":"Klinik fu\u0308r Kinder- und Jugendmedizin, DRK-Kliniken Berlin Westend, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Loew","sequence":"additional","affiliation":[{"name":"Kinderklinik Dritter Orden, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaughan","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Royal Devon and Exeter Foundation Trust, Exeter, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian","family":"Ellard","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T.","family":"Hattersley","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031220234014500_R1","doi-asserted-by":"crossref","unstructured":"Edghill EL, Dix RJ, Flanagan SE, Bingley PJ, Hattersley AT, Ellard S, Gillespie KM: HLA genotyping supports a nonautoimmune etiology in patients diagnosed with diabetes under the age of 6 months. 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