摘要目的 总结1例儿童免疫缺陷、着丝粒不稳定、面部异常(ICF)综合征的临床及基因突变特征并进行文献复习.方法 回顾性总结2016年12月青岛市妇女儿童医院肾脏免疫科收治的1例ICF综合征患儿的临床诊疗随访过程和基因测序结果,并以“ICF综合征”“免疫缺陷、着丝粒不稳定、面部异常”“DNMT3B基因”“ICF syndrome”“ICF syndrome and DNMT3B”为检索词,检索建库至2018年3月中文数据库(中国知网数据库、万方数据库)及PUBMED数据库进行文献复习.结果 患儿女,1岁10月龄,因反复感染1年余入院.体格检查发现眼距略宽,低耳位,余未见明显异常.辅助检查:IgG(＜1.34 g/L)、IgA (＜0.060 g/L)、IgM(＜0.179 g/L)均明显低于正常,淋巴细胞亚群六项检测基本正常(总T淋巴细胞:0.503、辅助性T细胞:0.328、杀伤T细胞:0.166、自然杀伤细胞:0.184、总B淋巴细胞:0.276).基因检测示:DNMT3B基因复合杂合突变,第8内含子c.922-2A＞G (IVS8-2A＞G)杂合剪切位点突变和第23外显子c.2477G＞A (P.R826H)杂合错义突变.患儿染色体分析:46,XX,分析100个核型其中64个核型存在1号染色体着丝粒不稳定现象.检索符合条件的中文文献0篇,英文文献5篇,共有29例因DNMT3B基因突变导致ICF综合征的患者;有43个突变位点与ICF综合征发病有关,包括34个错义突变,2个缺失突变,1个插入突变,6个内含子突变;其中11例为复合杂合突变.所有患者均有染色体着丝粒不稳定现象,面容发育异常,以眼距增宽和耳位低多见,大多数患者有语言、运动发育延迟,少数伴有智力障碍,辅助检查以体液免疫缺陷为主.结论 ICF综合征为罕见的常染色体隐性遗传原发性免疫缺陷病,具有典型的临床三联征,基因检测可进一步明确诊断.本例患儿DNMT3B基因突变为未报道的新突变.

abstractsObjective To analyze the clinical and genetic features of immunodeficiency,centromeric instability,and facial anomalies (ICF) syndrome with a case report and literature review.Methods 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.Results 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.Conclusions 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.