Department of Pediatrics, First Affiliated Hospital of Hunan Normal University/Hunan Provincial People's Hospital, Changsha, China.
Department of Biochemistry, School of Basic Medical Science, Chengde Medical University, Chengde, China.
Front Cell Infect Microbiol. 2021 Mar 15;11:605589. doi: 10.3389/fcimb.2021.605589. eCollection 2021.
This study presents a relatively rare case of disseminated () infection in an HIV-negative patient.
An 8-month-old girl was hospitalized because of uncontrollable fever and cough for 6 days. Routine laboratory tests, biochemical detection, immunological tests, pathogenic examination, and imaging inspection were performed. Genetic tests of trio whole genome sequencing (Trio-WES), trio copy number sequencing (Trio-CNVseq), and Sanger sequencing were conducted to identify pathogenic variants. analysis of the sequence alignment and structural modeling results was carried out to study the possible pathogenicity of the identified variant. Western blotting was performed to investigate the expression of the identified gene at the protein level.
Enhanced CT and MRI scanning demonstrated thymic dysplasia, diffuse pulmonary and liver nodules, and many balloon-like air sacs in both lungs. The white blood cell count, neutrophil count, and neutrophil ratio were normal or elevated. The patient was HIV-negative and bone marrow and blood culture showed infection. Total lymphocyte count, CD3+ T lymphocyte count, CD3+CD4+ T lymphocyte count, CD3+CD8+ T lymphocyte count, and NK cell count decreased, while the number of CD19 positive B cells increased. However, the ratio of CD3+CD4+:CD3+CD8+ T cells increased. Trio-WES identified a homozygous private variant of NM_006509: c.400_c.401insAGC/p.Lys134 delinsLysGln in and Sanger sequencing validated the result. Structural modeling indicated that the variant may be pathogenic. Reverse transcription-polymerase chain reaction and Western blot analysis showed that the expression of RelB in the patient was lower than that in the healthy controls at mRNA and protein levels.
This is the first report on disseminated infection in a patient with a homozygous private variant of .
本研究报告了一例 HIV 阴性患者中罕见的播散性 （）感染病例。
一名 8 月龄女婴因持续 6 天高热、咳嗽而住院。进行了常规实验室检查、生化检测、免疫检查、病原学检查和影像学检查。对三人体全基因组测序（Trio-WES）、三人体拷贝数测序（Trio-CNVseq）和 Sanger 测序的基因进行了遗传检测，以鉴定致病变异。对序列比对和结构建模结果进行了分析，以研究鉴定变异的可能致病性。通过 Western blot 法检测鉴定基因在蛋白水平的表达情况。
增强 CT 和 MRI 扫描显示胸腺发育不良，弥漫性肺部和肝脏结节，双肺有许多气球样气囊。白细胞计数、中性粒细胞计数和中性粒细胞比例正常或升高。患者 HIV 阴性，骨髓和血培养显示 感染。总淋巴细胞计数、CD3+T 淋巴细胞计数、CD3+CD4+T 淋巴细胞计数、CD3+CD8+T 淋巴细胞计数和 NK 细胞计数降低，而 CD19 阳性 B 细胞数量增加。然而，CD3+CD4+：CD3+CD8+T 细胞的比例增加。Trio-WES 鉴定出 基因的纯合私有变异 NM_006509：c.400_c.401insAGC/p.Lys134 delinsLysGln，Sanger 测序验证了结果。结构建模表明，该变异可能具有致病性。逆转录-聚合酶链反应和 Western blot 分析显示，患者 RelB 在 mRNA 和蛋白水平的表达均低于健康对照者。
这是首例报道的携带 基因纯合私有变异的患者发生播散性 感染。
