title: X-chromosome inactivation analysis in a female carrier of FOXP3 mutation.
abstract: Immune dysregulation, polyendocrinopathy and enteropathy with X-linked inheritance (IPEX) is a serious disease arising from mutations in FOXP3. This gene codifies for a transcription factor whose dysfunction results in hyperactivation of T cells. It is not clear, however, why an intermediate phenotype is not seen in heterozygous females, who are completely healthy. In order to address this question, we investigated X-chromosome inactivation in peripheral blood lymphocytes from a heterozygous female with a child affected by IPEX. No preferential inactivation was shown in freshly sorted CD4+, CD8+, CD19+ cells or in IL-2 cultured CD4 and CD8 T cells, indicating that peripheral blood lymphocytes in these women are randomly selected. Moreover, only one single FOXP3 transcript was expressed by CD4 T cell clones analysed by RT-PCR, confirming that this gene is subject to X- inactivation. We hypothesize that hyper-activation of T cell in carriers of FOXP3 mutations is regulated by the presence of normal regulatory T cells.
authors.affiliation: Department of Sciences of Reproduction and Development IRCCS Burlo Garofolo, Trieste, Italy. tommasin@burlo.trieste.it
authors.forename: A
authors.initials: A
authors.lastname: Tommasini
authors.forename: S
authors.initials: S
authors.lastname: Ferrari
authors.forename: D
authors.initials: D
authors.lastname: Moratto
authors.forename: R
authors.initials: R
authors.lastname: Badolato
authors.forename: M
authors.initials: M
authors.lastname: Boniotto
authors.forename: D
authors.initials: D
authors.lastname: Pirulli
authors.forename: L D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: M
authors.initials: M
authors.lastname: Andolina
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002648:Child; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D003967:Diarrhea / Q000235:genetics; D004303:Dosage Compensation, Genetic; D004700:Endocrine System Diseases / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology*; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D017354:Point Mutation; D013577:Syndrome
chemical_list: D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors