Hu S C, Wang Y B, Sun Q, Liu X R, Sun L L, Cui G M
Department of Nephrology and Immunology, Qingdao Women and Children's Hospital, Qingdao 266000, China.
Zhonghua Er Ke Za Zhi. 2019 Jan 2;57(1):55-59. doi: 10.3760/cma.j.issn.0578-1310.2019.01.013.
To analyze the clinical and genetic features of immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome with a case report and literature review. The clinical data and genetic test of a girl diagnosed with ICF syndrome in the Department of Nephrology and Immunology in Qingdao Women and Children's Hospital in December 2016 were extracted and analyzed. "ICF syndrome" "immunodeficiency, centromeric instability and facial anomalies syndrome" "ICF syndrome and DNMT3B" were used as key words to search Chinese databases and Pubmed for literature until March 2018, and the literature was reviewed. A female patient aged 22 months old with ocular hypertelorism and low-set ears was admitted due to recurrent infection over one year. Laboratory tests showed humoral immune deficiency with IgG<1.34 g/L, IgA<0.060 g/L, and IgM<0.179 g/L, but normal cellular immunity (total T lymphocyte 0.503, hepler T lymphocyte 0.328, cytotoxic T lymphocyte 0.166, natural killer cell 0.184, total B lymphocyte 0.276). Whole-exome sequencing revealed a de novo heterozygous splice site mutation c.922-2A>G in intron 8, and a de novo heterozygous missense mutation c.2477G>A in exon 23 of DNMT3B gene. Chromosome karyotype analysis showed 46, XX, with 64 out of 100 karyotypes showing centromere instability in chromosome 1. Five papers were found which were all in English, with total of 29 patients. Forty-three mutations were reported, including 34 missense, 2 deletion, 1 insertion, 6 splice site mutations. Eleven patients had complex heterozygosis mutations. All patients had centromere instability, humoral immune deficiency and facial dysplasia which were mainly ocular hypertelorism and low-set ears. Most patients had language and motor development delay, and a few were combined with mental retardation. ICF syndrome is a rare autosomal recessive primary immunodeficiency with classic clinical triad manifestations. De novo mutation of DNMT3B gene is one of etiologies according to genetic test.
通过病例报告和文献复习分析免疫缺陷、着丝粒不稳定和面部异常（ICF）综合征的临床和遗传特征。提取并分析了2016年12月在青岛妇女儿童医院肾内科和免疫科诊断为ICF综合征的一名女孩的临床资料和基因检测结果。以“ICF综合征”“免疫缺陷、着丝粒不稳定和面部异常综合征”“ICF综合征与DNMT3B”为关键词，检索中国数据库和Pubmed直至2018年3月的文献，并进行文献复习。一名22个月大的女性患者，因眼距增宽和低位耳，因反复感染1年入院。实验室检查显示体液免疫缺陷，IgG<1.34 g/L，IgA<0.060 g/L，IgM<0.179 g/L，但细胞免疫正常（总T淋巴细胞0.503，辅助性T淋巴细胞0.328，细胞毒性T淋巴细胞0.166，自然杀伤细胞0.184，总B淋巴细胞0.276）。全外显子测序显示DNMT3B基因第8内含子有一个新发杂合剪接位点突变c.922-2A>G，第23外显子有一个新发杂合错义突变c.2477G>A。染色体核型分析显示46, XX，100个核型中有64个显示1号染色体着丝粒不稳定。共找到5篇英文文献，涉及29例患者。报告了43个突变，包括34个错义突变、2个缺失突变、1个插入突变、6个剪接位点突变。11例患者有复合杂合突变。所有患者均有着丝粒不稳定、体液免疫缺陷和面部发育异常，主要为眼距增宽和低位耳。大多数患者有语言和运动发育迟缓，少数合并智力障碍。ICF综合征是一种罕见的常染色体隐性原发性免疫缺陷病，具有典型的临床三联征表现。根据基因检测，DNMT3B基因的新发突变是病因之一。
