کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5905127 | 1159836 | 2016 | 24 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Common variable immunodeficiency, impaired neurological development and reduced numbers of T regulatory cells in a 10-year-old boy with a STAT1 gain-of-function mutation
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کلمات کلیدی
FOXP3CMCGOFCVIDSTAT transcription factorSTAT - آمارT-regulatory cells - سلول های تنظیم کننده Tgain-of-function - سود عملکردcytokine signaling - سیگنالینگ سیتوکینSignal transducer and activator of transcription - مبدل سیگنال و فعال کننده رونویسیCVID, common variable immunodeficiency - نقص ایمنی متغیر شایعchronic mucocutaneous candidiasis - کاندیدیازیس مضطرب مزمنImmunodeficiency - کمبود ایمنی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
ژنتیک
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Common variable immunodeficiency, impaired neurological development and reduced numbers of T regulatory cells in a 10-year-old boy with a STAT1 gain-of-function mutation Common variable immunodeficiency, impaired neurological development and reduced numbers of T regulatory cells in a 10-year-old boy with a STAT1 gain-of-function mutation](/preview/png/5905127.png)
چکیده انگلیسی
Recently, gain-of-function (GOF) mutations in the gene encoding signal transducer and activator of transcription 1 (STAT1) have been associated with chronic mucocutaneous candidiasis (CMC). This case report describes a 10-year-old boy presenting with signs of common variable immunodeficiency (CVID), failure to thrive, impaired neurological development, and a history of recurrent mucocutaneous Candida infections. Sequencing of the STAT1 gene identified a heterozygous missense mutation in exon 7 encoding the STAT1 coiled-coil domain (c.514T > C, p.Phe172Leu). In addition to hypogammaglobulinemia with B-cell deficiency, and a low percentage of Th17 cells, immunological analysis of the patient revealed a marked depletion of forkhead-box P3+-expressing regulatory T cells (Tregs). In vitro stimulation of T cells from the patient with interferon-α (IFNα) and/or IFNɣ resulted in a significantly increased expression of STAT1-regulated target genes such as MIG1, IRF1, MX1, MCP1/CCL2, IFI-56K, and CXCL10 as compared to IFN-treated cells from a healthy control, while no IFNα/ɣ-mediated up-regulation of the FOXP3 gene was found. These data demonstrate that the STAT1 GOF mutation F172L, which results in impaired stability of the antiparallel STAT1 dimer conformation, is associated with inhibited Treg cell development and neurological symptoms.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gene - Volume 586, Issue 2, 25 July 2016, Pages 234-238
Journal: Gene - Volume 586, Issue 2, 25 July 2016, Pages 234-238
نویسندگان
Robin Kobbe, Manuela Kolster, Sebastian Fuchs, Ulf Schulze-Sturm, Jutta Jenderny, Lothar Kochhan, Julia Staab, Eva Tolosa, Bodo Grimbacher, Thomas Meyer,