STAT3基因自发突变致儿童高IgE综合征一家系研究  

A pedigree study on hyper-IgE syndrome caused by STAT3 gene spontaneous mutation in a child

作　　者：秦碧波 于建斌[1] 刘莉娜 王雪晴 QIN Bi-bo;YU Jian-bin;LIU Li-na;WANG Xue-qing(Department of Dermatology»the First A.ffiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China;Center of Hereditary and Prenatal Diagnosis,the First Af filiated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第一附属医院皮肤科,河南郑州450052 [2]郑州大学第一附属医院遗传与产前诊断中心,河南郑州450052

出　　处：《中华实用诊断与治疗杂志》2022年第4期330-333,共4页Journal of Chinese Practical Diagnosis and Therapy

基　　金：郑州大学遗传性皮肤病研究生联合培养基地建设项目(YJSCXJD201908)。

摘　　要：目的 分析1例高IgE综合征患儿临床表型及其致病基因突变和家系发病情况。方法 收集1例高IgE综合征患儿(先证者)与其家系的临床资料,采集先证者及其父母外周血,提取基因组DNA,采用高通量测序法对先证者皮肤病相关基因各外显子编码区域进行测序,确定基因变异位点,采用PCR-Sanger测序法验证致病基因变异情况,应用ClustalX 2.1软件分析突变位点的保守性。结果 先证者出生后2个多月时头面部、四肢出现片状红斑、丘疹、糜烂及疖肿,伴发鹅口疮;4个月时皮疹加重伴头皮脓肿形成;随后皮疹间断发作,持续1~4周缓解;1岁11个月时皮疹再发,伴发热、咳嗽,胸部CT显示右肺下叶脓肿形成;2岁时因肺脓肿加重行手术分次切除右侧病变肺叶。入院时实验室检查显示白细胞计数、外周血嗜酸性粒细胞比率、IgE水平升高,口角黏膜分泌物真菌镜检阳性。基因测序结果显示,先证者STAT3基因第13号外显子发生C→T杂合突变(c.1144C>T,p.R382W),导致编码蛋白第382位氨基酸由精氨酸变为色氨酸。家系中无类似患者,先证者父母该位点均未发现突变,先证者为自发突变。ClustalX 2.1软件分析结果显示,STAT3蛋白在5个物种382位氨基酸序列中呈完全保守,提示突变具有致病意义。依据患者临床表现、辅助检查、基因检测与家系分析,诊断为高IgE综合征。给予抗过敏、抗感染、提高免疫力及手术等治疗,病情基本控制,目前随访中。结论 STAT3基因c.1144C>T(p.R382W)杂合突变是引起该先证者临床表型的可能原因。Objective To analyze the clinical phenotype pathogenic gene mutation in a child with hyper-IgE syndrome and pedigree incidence. Methods The clinical data of the proband of hyper-IgE syndrome and his family were collected. The peripheral blood samples and genomic DNA were obtained from the proband and his parents. The coding regions of exons of skin disease-related genes of the proband were sequenced by high-throughput sequencing to determine the gene variation sites, and PCR-Sanger sequencing was used to verify the pathogenic gene variation. Clustalx 2.1 software was used to analyze the conservation of mutation sites. Results The proband developed flaky erythema, papules, erosion and furuncles on the head, face and limbs, accompanied by thrush in over 2 months after birth. In 4 months, the rash worsened and the skin abscess formed on the head, and was relieved 1 to 4 weeks later after intermittent onset. The rash recurred at the age of 1 year and 11 months, accompanied by fever and cough, and the abscess in the lower lobe of the right lung on CT. At the age of 2 years, fractional resection of the right diseased lobe was performed due to the aggravation of lung abscess. Laboratory examination showed that the leukocyte count, peripheral blood eosinophils and IgE increased significantly, and the fungal microscopic examination of oral and lip mucosal secretions was positive. Gene sequencing showed that the proband had a C→T heterozygous mutation in exon 13 of STAT3 gene(c.1144 C>T,p.R382 W), inducing the change of the amino acid 382 of the coding protein from arginine to tryptophan. There was no similar patient in the family. No mutation was found at this site in the parents of the proband, and the proband was proved spontaneous mutation. Clustalx 2.1 software analysis showed that STAT3 protein was completely conserved at amino acid 382 in 5 species, which suggested a pathogenic mutation. The final diagnosis of hyper-IgE syndrome was made on the basis of clinical manifestations, auxiliary examinations, gene detecti

关 键 词：高IGE综合征 湿疹 感染 STAT3基因 

分 类 号：R725.9[医药卫生—儿科]