title: Fetal-onset IPEX: report of two families and review of literature.
abstract: Early-life autoimmunity is an IPEX characteristic, however intrauterine forms had not yet been described. Here, two unrelated families with clear evidence of fetal-onset IPEX are reported. One had 5 miscarriages of males in two generations, and a newborn presenting type-1 diabetes mellitus immediately after birth, diarrhea, thrombocytopenia, eczematous dermatitis, eosinophilia, high IgE levels and autoantibodies to pancreatic islet antigens at 4-days-old. Maternal serology was negative. He presented a FOXP3 mutation, c.1189C>T, p.Arg397Trp, previously described only in another family with IPEX at birth. The second family had several miscarriages of males in three consecutive generations and a novel FOXP3 c.319_320delTC mutation was observed in two miscarried monochorionic twin male fetuses. These twins died at 21weeks of gestation due to hydrops, and CD3+ infiltrating lymphocytes were found in their pancreas. We demonstrate that: i) IPEX may develop in fetal life; and ii) c.1189C>T and c.319_320delTC mutations are associated with early-onset phenotype.
authors.affiliation: Universidade Estadual de Londrina (UEL), Londrina, PR, Brazil.
authors.forename: Mariana Moraes
authors.initials: MM
authors.lastname: Xavier-da-Silva
authors.affiliation: Department of Pediatrics, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Moreira-Filho
authors.affiliation: Faculdade de Medicina Estadual de Marilia (FAMEMA), Marília, SP, Brazil.
authors.forename: Edson
authors.initials: E
authors.lastname: Suzuki
authors.affiliation: Dept of Pathology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
authors.forename: Francy
authors.initials: F
authors.lastname: Patricio
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Antonio
authors.initials: A
authors.lastname: Coutinho
authors.affiliation: Department of Pediatrics, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil. Electronic address: magdascs@usp.br.
authors.forename: Magda
authors.initials: M
authors.lastname: Carneiro-Sampaio
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D003922:Diabetes Mellitus, Type 1 / Q000151:congenital; D003967:Diarrhea; D005315:Fetal Diseases / Q000235:genetics* / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000276:immunology / Q000401:mortality; D006801:Humans; D007154:Immune System Diseases / Q000151:congenital; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: FOXP3; Fetal IPEX; Fetal hydrops; Miscarriages; Primary immunodeficiency; Type I diabetes mellitus