7例HIV阴性马尔尼菲篮状菌感染患者基因变异分析及临床特征

Genomic variant analysis and clinical characteristics analysis of 7 patients with HIV⁃negative Talaromyces marneffei infection

目的分析人类免疫缺陷病毒(HIV)阴性马尔尼菲篮状菌感染患者基因组中非同义单核苷酸变异的情况及其临床特征,为临床诊断提供新思路。方法收集2018年1月-2021年7月深圳市第三人民医院感染科收治的HIV阴性马尔尼菲篮状菌感染患者的血样和临床资料,利用全外显子测序分析基因组中抗真菌相关基因突变的情况,并比较单核苷酸突变患者和无突变患者的临床特征。结果在入组的7例患者基因组中,有4例检测出不同基因位点突变,占57.14%。患者1的STAT1基因发生杂合子突变,c.G1053T,p.L351F;患者2的JAK2基因发生杂合突变,c.C1144T,p.H382Y;患者3的TYK2基因发生杂合突变,c.G2102C,p.R701T;患者5的ARIE基因发生杂合突变,c.C1634T,p.S545F。经遗传变异分析与数据库比对,上述的基因突变存在临床致病可能。对单核苷酸突变患者和无突变患者的临床特征和实验室检查结果进行对比发现,该两组在临床特点和实验室指标方面无明显差异。结论HIV阴性马尔尼菲篮状菌感染患者中存在可能的致病性基因突变,但根据临床特征很难鉴别患者是否具有原发性免疫缺陷,应加强对该类患者的基因突变检测,优化治疗方案,减缓疾病进展。

Objective To analyze the non⁃synonymous single nucleotide variations(nsSNV)and their clinical characteristics in human immunodeficiency virus(HIV)⁃negative patients with Talaromyces marneffei infection,which to provide new ideas for clinical diagnosis.Methods The blood samples and clinical data of HIV⁃negative patients with T.marneffei infection admitted to the Department of Infectious Diseases of Shenzhen Third People's Hospital from January 2018 to July 2021 were collected.Whole exome sequencing was used to analyze the mutations of antifungal related genes in the genome,and the clinical characteristics of patients with single nucleotide mutations and those without mutations were compared.Results Among the 7 patients,4 patients(57.14%)had different gene mutations.Patient 1 carried a heterozygous mutation in STAT1 gene(c.G1053T,p.L351F),and patient 2 carried a heterozygous mutation in JAK2 gene(c.C1144T,p.H382Y),Patient 3 had a heterozygous mutation in TYK2 gene(c.G2102C,p.R701T),and patient 5 had a heterozygous mutation in ARIE gene(c.C1634T,p.S545F).Through genetic variation analysis and database comparison,the above gene mutations might lead to clinically pathogenic.There was no significant difference in the clinical characteristics and laboratory test results between the patients with single nucleotide mutations and those without mutations.Conclusions There were possible pathogenic gene mutations in HIV⁃negative patients with T.marneffei infection,but it was difficult to identify whether the patients had primary immunodeficiency according to their clinical characteristics.Therefore,it should be necessary to strengthen the detection of gene mutations in these patients and optimize the treatment plan to slow the progression of the disease.