Clinical and molecular profile of a new series of patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome: inconsistent correlation between forkhead box protein 3 expression and disease severity.
Clinical and molecular profile of a new series of patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome: inconsistent correlation between forkhead box protein 3 expression and disease severity.
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DOI：
10.1016/j.jaci.2008.09.027
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发表时间：
2008-12-01
期刊：
影响因子：
--
通讯作者：
Bacchetta, Rosa
中科院分区：
文献类型：
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作者：
Gambineri, Eleonora;Perroni, Lucia;Bacchetta, Rosa
背景技术背景：免疫失调、多内分泌病、肠病、X连锁综合征（Immune dysregulation，polyendocrinopathy，enteropathy，X-linked，IPEX）是由免疫耐受的关键调节因子叉头盒蛋白3（forkhead box protein 3，FOXP 3）基因突变引起的自身免疫性遗传病。在14名根据FOXP 3基因测序诊断为IPEX综合征的无关受影响男性受试者中，我们确定了特定FOXP 3突变是否影响FOXP 3蛋白表达，并将分子和临床数据相关联。14例受试者的FOXP 3分子分析显示13个错义和剪接位点突变，包括7个新突变。肠病，通常与内分泌病和湿疹，在所有患者中报告，特别是在那些携带FOXP 3功能结构域内的突变或突变，改变蛋白质表达。然而，相似的基因型并不总是导致疾病表现和严重程度方面相似的表型。此外，FOXP 3蛋白表达与疾病严重程度无关。结论：严重的自身免疫性肠病，这往往是与IgE水平升高和嗜酸性粒细胞增多，是最突出的早期表现IPEX综合征。然而，病程是可变的，有些不可预测。因此，应始终进行FOXP 3的遗传分析以确保准确诊断，FOXP 3蛋白表达分析不应是IPEX综合征的唯一诊断工具。
BACKGROUND: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is an autoimmune genetic disorder caused by mutation of the forkhead box protein 3 gene (FOXP3), a key regulator of immune tolerance.OBJECTIVE: We sought to provide clinical and molecular indicators that facilitate the understanding and diagnosis of IPEX syndrome.METHODS: In 14 unrelated affected male subjects who were given diagnoses of IPEX syndrome based on FOXP3 gene sequencing, we determined whether particular FOXP3 mutations affected FOXP3 protein expression and correlated the molecular and clinical data.RESULTS: Molecular analysis of FOXP3 in the 14 subjects revealed 13 missense and splice-site mutations, including 7 novel mutations. Enteropathy, generally associated with endocrinopathy and eczema, was reported in all patients, particularly in those carrying mutations within FOXP3 functional domains or mutations that altered protein expression. However, similar genotypes did not always result in similar phenotypes in terms of disease presentation and severity. In addition, FOXP3 protein expression did not correlate with disease severity.CONCLUSION: Severe autoimmune enteropathy, which is often associated with increased IgE levels and eosinophilia, is the most prominent early manifestation of IPEX syndrome. Nevertheless, the disease course is variable and somewhat unpredictable. Therefore genetic analysis of FOXP3 should always be performed to ensure an accurate diagnosis, and FOXP3 protein expression analysis should not be the only diagnostic tool for IPEX syndrome.