Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome)
Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome)
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DOI：
10.1136/jmg.2007.053397
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发表时间：
2008-02-01
影响因子：
4
通讯作者：
Weemaes, C. M. R.
中科院分区：
文献类型：
--
作者：
Hagleitner, M. M.;Lankester, A.;Weemaes, C. M. R.
背景：免疫缺陷、着丝粒不稳定和面部畸形(ICF综合征)是一种罕见的常染色体隐性遗传病，其特征是面部畸形、免疫球蛋白缺陷以及PHA刺激淋巴细胞后1、9和16号染色体的分支。小部分基因组DNA低甲基化是ICF患者的一种罕见特征，部分ICF患者的DNA甲基转移酶基因Dnmt3b突变可解释其原因。目的：全面了解ICF患者的临床特征以及ICF患者的基因表型相关性。方法：通过文献检索获得ICF患者的数据，并通过对相关作者的问卷调查获得更多信息。结果与结论：45例患者均为已证实的着丝粒不稳定患者。面部畸形是一个常见的特征(n=41/42)，尤其是内上睑皱褶、外翻、鼻梁平坦和耳垂。几乎所有患者都有低丙种球蛋白血症或无丙种球蛋白血症(n=39/44)。在几名患者中发现了机会性感染，这表明T细胞功能障碍。两名患者被记录为血液学恶性肿瘤。ICF患者的预期寿命很低，特别是那些在婴儿期有严重感染或慢性胃肠道问题并无法茁壮成长的人。ICF的早期诊断很重要，因为早期补充免疫球蛋白可以改善病程。异基因干细胞移植应该被认为是严重感染或无法茁壮成长的患者的一种治疗选择。在34名患者中，只有19人出现Dnmt3b突变，这表明存在遗传异质性。Dnmt3b突变的患者与无Dnmt3b突变的患者之间没有发现基因-表型相关性。
Background: Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a rare autosomal recessive disease characterised by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after PHA stimulation of lymphocytes. Hypomethylation of DNA of a small fraction of the genome is an unusual feature of ICF patients which is explained by mutations in the DNA methyltransferase gene DNMT3B in some, but not all, ICF patients.Objective: To obtain a comprehensive description of the clinical features of this syndrome as well as genotype phenotype correlations in ICF patients.Methods: Data on ICF patients were obtained by literature search and additional information by means of questionnaires to corresponding authors.Results and conclusions: 45 patients all with proven centromeric instability were included in this study. Facial dysmorphism was found to be a common characteristic (n = 41/42), especially epicanthic folds, hypertelorism, flat nasal bridge and low set ears. Hypo- or agammaglobulinaemia was demonstrated in nearly all patients (n = 39/44). Opportunistic infections were seen in several patients, pointing to a T cell dysfunction. Haematological malignancy was documented in two patients. Life expectancy of ICF patients is poor, especially those with severe infections in infancy or chronic gastrointestinal problems and failure to thrive. Early diagnosis of ICF is important since early introduction of immunoglobulin supplementation can improve the course of the disease. Allogeneic stem cell transplantation should be considered as a therapeutic option in patients with severe infections or failure to thrive. Only 19 of 34 patients showed mutations in DNMT3B, suggesting genetic heterogeneity. No genotype-phenotype correlation was found between patients with and without DNMT3B mutations.