A novel FOXP3 mutation causing fetal akinesia and recurrent male miscarriages

Rae, William; Gao, Yifang; Bunyan, David J.; Holden, Samantha; Gilmour, Kimberly; Patel, Sanjay; Wellesley, Diana; Williams, Anthony P.

doi:10.1016/j.clim.2015.09.006

Cited by 24 publications

(42 citation statements)

References 10 publications

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“…A rare Xlinked disorder of IPEX syndrome with dysregulated autoimmunity and antimicrobial immunity is caused by mutations of FOXP3 [2][3][4][5][6][7][8][9] . FOXP3 is an important transcription factor for the development and function of regulatory T cells (Treg), and the expression of this protein in Treg was found to be decreased in patients with FOXP3 mutations [3][4][5]9) .…”

Section: Discussionmentioning

confidence: 99%

“…Phenotypic spectrums of IPEX syndrome are broad, ranging from mild forms with one or two phenotypes of the triad, to typical form without an eventful perinatal history and more severe fetal/neonatal form [2][3][4][5][6][7][8][9] . Additional organ dysfunctions include autoimmune hematologic disorders (in about 50% of cases), renal diseases (in about 33%), and autoimmune hepatitis, recurrent infection, serositis, and neurologic abnormalities [2][3][4][5][6][7][8][9] .…”

Section: Discussionmentioning

confidence: 99%

“…Such mutations have been found in young children with the rare and life threatening disease of immune dysregulation, polyendocrinopathy, enteropathy, Xlinked (IPEX) syndrome, whose clinical triad comprises (i) chronic enteropathy resulting in protracted diarrhea, (ii) eczematous dermatitis, and (iii) autoimmune endocrinopathy such as type 1 diabetes mellitus (DM) and thyroiditis [2][3][4][5][6][7][8][9] . However, many patients with FOXP3 mutations exhibit growth and developmental problems, and some have seizures and hypotonia [2][3][4][5][6] .…”

Section: Introductionmentioning

confidence: 99%

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FOXP3 Mutation in a Patient with Proportional Microcephaly and Developmental Delay

cho¹,

최가은²,

김영옥³

et al. 2017

journalofthekoreanchildneurologysociety

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Most cases of microcephaly with growth failure and developmental delay have a genetic or metabolic etiology. Whole-exome sequencing (WES) has uncovered many causative genes and has also broadened their phenotypic spectrum. The present study applied WES to a boy with microcephaly, growth failure, developmental delay, seizures and atopic dermatitis, which reveal an unexpected frame-shift mutation (c.1248_1253delinsCT, NM_014009.3; p.Lys416Asnfs, NP_054728.2) in the forkhead box P3 gene (FOXP3). Mutations of this gene are known to result in immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Mutation of FOXP3 was reverified by Sanger sequencing in the proband and his carrier mother. Flow-cytometry expression study of FOXP3 in peripheral white blood cells showed that the mean fluorescence intensity of FOXP3 was lower in the proband than in a normal control. We report a mild form of IPEX syndrome without chronic protracted diarrhea or major infections, instead presenting with proportional microcephaly, growth failure, developmental delay, seizures and atopic dermatitis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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FOXP3 Mutation in a Patient with Proportional Microcephaly and Developmental Delay

cho¹,

최가은²,

김영옥³

et al. 2017

journalofthekoreanchildneurologysociety

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“…Известно, что для матерей пациентов с IPEX-син-дромом характерно наличие многократных эпи-зодов спонтанных прерываний беременности при вынашивании плодов мужского пола [14,17,19]. В описанном случае анамнез матери пациента (но-сительницы мутации) также был отягощен невына-шиванием беременности на ранних сроках.…”

Section: к линический с лу чайunclassified

Neonatal Diabetes Mellitus in the Structure of IPEX Syndrome

et al. 2017

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This disease is characterized by the onset of primary immunodeficiency, which expresses itself as autoimmune multisystem failure, often clinically manifests during the first year of life; there are only about 150 cases in the world described by now. IPEX syndrome is caused by FOXP3 gene defect, which is a transcription factor that affects the activity of regulatory T-cells responsible for the maintenance of aytotolerance. There are around 70 pathogenic mutations in this gene described so far. Most patients with IPEX-syndrome have a clinical manifestations of the disease in the early neonatal period or during the first 3-4 months of life. For this disease the following clinical triad of manifestations is typical: Autoimmune enteropathy (100%), diabetes mellitus (70%), skin lesions (65%), as in the syndrome structure includes severe developmental delay (50%), thyroid disease (30%), recurrent infections (20%), rarer autoimmune cytopenia (Coombs-positive hemolytic anemia), pneumonia, nephritis, hepatitis, artrit, myositis, alopecia. However, some cases of later manifestations were described (in patients of more than 1 year of age) when patients did not show all clinical and laboratory symptoms typical for severe forms of the disease. Due to the severity of the disease and the high mortality in this group of patients, it is very important to diagnose it early and start therapy timely. The article describes a clinical case of permanent neonatal diabetes mellitus in the structure of IPEX syndrome.

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“…Although heterogeneous, the majority of IPEX syndrome patients have onset of disease in infancy [d’Hennezel et al, 2012; Barzaghi et al, 2012; Baris et al, 2014]. Recently, five families were described with fetuses with IPEX syndrome; prenatal clinical findings included hydrops, intrauterine growth restriction (IUGR), and prematurity [Reichert et al, 2015; Xavier-da-Silva et al, 2015; Rae et al, 2015; Vasiljevic et al, 2015]. Here, we present two novel inherited frameshift mutations in FOXP3 that introduce premature stop codons and cause fetal forms of IPEX syndrome.…”

Section: Introductionmentioning

confidence: 99%

Novel pathogenic variants in FOXP3 in fetuses with echogenic bowel and skin desquamation identified by ultrasound

Louie

Tan

Gilner

et al. 2017

American J of Med Genetics Pt A

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Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome is a rare, X-linked recessive disease that affects regulatory T cells (Tregs) resulting in diarrhea, enteropathy, eczema, and insulin-dependent diabetes mellitus. IPEX syndrome is caused by pathogenic alterations in FOXP3 located at Xp11.23. FOXP3 encodes a transcription factor that interacts with several partners, including NFAT and NF-κB, and is necessary for the proper cellular differentiation of Tregs. Although variable, the vast majority of IPEX syndrome patients have onset of disease during infancy with severe enteropathy. Only five families with prenatal presentation of IPEX syndrome have been reported. Here, we present two additional prenatal onset cases with novel inherited frameshift pathogenic variants in FOXP3 that generate premature stop codons. Ultrasound findings in the first patient identified echogenic bowel, echogenic debris, scalp edema, and hydrops. In the second patient, ultrasound findings included polyhydramnios with echogenic debris, prominent fluid-filled loops of bowel, and echogenic bowel. These cases further broaden the phenotypic spectrum of IPEX syndrome by describing previously unappreciated prenatal ultrasound findings associated with the disease.

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A novel FOXP3 mutation causing fetal akinesia and recurrent male miscarriages

Abstract: A novel FOXP3 mutation causing fetal akinesia and recurrent male miscarriages, Clinical Immunology (2015),

Cited by 24 publications

References 10 publications

FOXP3 Mutation in a Patient with Proportional Microcephaly and Developmental Delay

FOXP3 Mutation in a Patient with Proportional Microcephaly and Developmental Delay

Neonatal Diabetes Mellitus in the Structure of IPEX Syndrome

Novel pathogenic variants in FOXP3 in fetuses with echogenic bowel and skin desquamation identified by ultrasound

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