Blau综合征NOD2/CARD15基因突变及临床特征分析  

Analysis of NOD2/CARD15 Gene Mutation and Clinical Features in Blau Syndrome

作　　者：张高磊[1] 顾菲[1] 苏伟[1] 杨明[1] 张升[1] 蒋丽潇[1] 朱芸 秦琴 曹会娜 李倩 刘晓雁[1] ZHANG Gaolei;GU Fei;SU Wei;YANG Ming;ZHANG Sheng;JIANG Lixiao;ZHU Yun;QIN Qin;CAO Huina;LI Qian;LIU Xiaoyan(Department of Dermatology,Capital Institute of Pediatrics,Beijing 100020,China)

机构地区：[1]首都儿科研究所附属儿童医院皮肤科,北京100020

出　　处：《中国皮肤性病学杂志》2021年第8期849-854,共6页The Chinese Journal of Dermatovenereology

基　　金：国家自然科学基金(81974473,82073461)。

摘　　要：目的回顾总结4个Blau综合征家系先证者患儿及其父母NOD2/CARD15基因突变及临床特征。方法采用PCR扩增4个家系所有成员的NOD2/CARD15基因所有外显子。Sanger法测序NOD2基因所有外显子序列,Ensembl和NCBI dbSNP基因数据库比对确定致病位点,根据ACMG指南判定基因变异的致病性。对先证者患儿及其父母行查体及病史问诊。结果所有先证者患儿均检测到NOD2基因突变,家系1和3检测到NOD2基因突变c.1000C>T p.R334W,突变分别来源于父亲和母亲;家系2检测到NOD2基因突变c.956G>A p.G319E,突变为自发性;家系4检测到NOD2基因突变c.1469G>T p.W490L,突变来源于其母亲。所有先证者患儿均有不同程度皮肤、眼及关节损害,其中3/4患儿伴有智力及体格发育迟缓,2/4患儿伴有频繁发热,1/4患儿伴有肝肿大。家系1先证者父亲、家系3和4先证者母亲均有不同程度眼睛和关节损害。结论Blau综合征均由NOD2/CARD15基因突变,突变位于第四外显子,发病符合显性遗传;患儿除了具有Blau综合征的临床三联征,还具有其他临床特征。Objective To retrospectively analyze the mutations of NOD2/CARD15 gene and clinical features in 4 pedigree with Blau syndrome.Methods All exons of NOD2/CARD15 gene were amplified by PCR for everyone in 4 pedigree and the results were sequenced by Sanger,the pathogenic sites were identified by comparing Ensembl and NCBI dbSNP gene databases,the pathogenicity of gene variation was determined according to ACMG guidelines.Physical examination and medical history were performed on the proband and his parents.Results Mutations of NOD2/CARD15 gene were found in all probands.Mutations of c.1000 C>T p.R334W were found in pedigree 1 and 3,which originated from their father and mother respectively;spontaneous mutations of c.956G>A p.G319E was detected in pedigree 2,mutations of c.1469G>T p.W490I were found in pedigree 4,which originated from their mother.All the probands had different levels damage of skin,eye and joint,of which 3/4 had mental and physical retardation,2/4 had frequent fever,and 1/4 had hepatomegaly.The father of proband in pedigree 1 and the mother of proband in pedigree 3 and 4 had damage of eye and joint.Conclusion Blau syndrome is a dominant inheritance disease and caused by NOD2/CARD15 gene mutation,which is located in the fourth exon.In addition to the clinical triad of Blau syndrome,the children also have other clinical characteristics.

关 键 词：Blau综合征 NOD2/CARD15基因 基因突变 遗传 临床特征 

分 类 号：R725.9[医药卫生—儿科]