Clinical Heterogeneity in Patients With FOXP3 Mutations Presenting With Permanent Neonatal Diabetes

• DOI: 10.2337/dc08-1188
• Publication Date: 2008-10-18T00:59:31Z
• Authors: Oscar Rubio-Cabezas; Jayne A.L. Minton; Richard Caswell; Julian P. Shield; Dorothee Deiss; Zdenek Sumnik; Amely Cayssials; Mathias Herr; Anja Loew; Vaughan Lewis; Sian Ellard; Andrew T. Hattersley
• Keywords: Immune Dysregulation

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is caused by FOXP3 mutations. We aimed to determine the prevalence, genetics, and clinical phenotype of mutations in a large cohort with permanent neonatal diabetes (PNDM).The 11 coding exons polyadenylation region were sequenced 26 male subjects diagnosed before 6 months age whom common genetic causes PNDM had been excluded. Ten at least one additional immune-related disorder, remaining 16 isolated diabetes.We identified four hemizygous 10 patients associated disorders 0 (P = 0.002). Three two novel (R337Q P339A) previously reported L76QfsX53 developed classic IPEX died within first 13 months. The mutation V408M was found three from unrelated families mild hypothyroidism autoimmune enteropathy (n 2) or nephrotic 1) survival 12-15 years.FOXP3 result approximately 4% cases Patients not only have but, unexpectedly, may more benign phenotype. sequencing should be performed any patient diagnosis who develops other possible autoimmune-associated conditions, even absence full syndrome.