Clinical–alimentary tractSevere Food Allergy as a Variant of IPEX Syndrome Caused by a Deletion in a Noncoding Region of the FOXP3 Gene
Section snippets
Patients IV.1 and IV.2
Patient IV.1, (Figure 1) the index case, followed at Necker-Enfants Malades Hospital, Paris, was born in 2000 after an uneventful pregnancy to unrelated, healthy white parents. No abnormalities were observed during the neonatal period while he was exclusively breastfed. At 3 weeks of age, infant formula was introduced, and, within 1 week, he developed massive watery-bloody diarrhea requiring total parenteral nutrition, daily albumin supplementation, and repeated blood transfusions. The severe
Isolation of Peripheral Blood Mononuclear Cells
Peripheral blood mononuclear cells (PBMC) were isolated from whole blood using Ficoll-Paque gradient centrifugation as previously described.5
Sequence Analysis of FOXP3
Genomic DNA (gDNA) was isolated from whole blood using the QIAamp DNA Blood Mini Kit (Qiagen, Valencia, CA) according to the manufacturer’s protocol. Each of the 11 coding exons of FOXP3 including intron/exon boundaries and the region surrounding the first polyadenylation signal were amplified from gDNA by polymerase chain reaction (PCR) using intronic
Genetic Analysis
The human FOXP3 gene consists of 11 protein-coding exons (exons 1–11) as well as a noncoding exon (exon −1) located 6 kilobases (kb) upstream of exon 1 (Figure 3). All mutations of the FOXP3 gene identified to date are located within, or adjacent to, one of the 11 translated exons or within the first polyadenylation site. Based on the clinical phenotype observed in affected members of this family, we sequenced exons 1–11 of the FOXP3 gene, including all intron/exon boundaries and the first
Discussion
The family reported here presented with an atypical form of IPEX syndrome that was characterized by multiple severe food allergies associated with AIE. The patients also had eczema, hyper-IgE, and eosinophilia but, unlike most other cases of IPEX syndrome, did not present with endocrinopathy or cytopenia. The restricted symptomatology observed in the affected members of this family demonstrates the clinical heterogeneity of the IPEX syndrome and expands the range of patients for whom IPEX
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Supported by NIH grants HD37091 (to H.D.O.) and HD043376-03 (to T.R.T.), Jeffrey Modell Foundation grant (to H.D.O.), Immunodeficiency Foundation grant (to H.D.O.), INSERM and the Association Francois Aupetit grants (to F.R.), and by a scholarship of the European Leonardo da Vinci Foundation (to N.M.).
Conflict of interest statement: The authors declare no conflicts of interest.