两种新型复合杂合功能缺失突变导致胎儿IRAK-4缺乏症,并伴有绿脓杆菌败血症。

IF 4.5 3区 医学 Q2 IMMUNOLOGY Clinical immunology Pub Date : 2024-06-03 DOI:10.1016/j.clim.2024.110268
Fang Zhang , Zhiwei Wang , Shuai Men, Jinglu Zhang, Leilei Wang
{"title":"两种新型复合杂合功能缺失突变导致胎儿IRAK-4缺乏症,并伴有绿脓杆菌败血症。","authors":"Fang Zhang ,&nbsp;Zhiwei Wang ,&nbsp;Shuai Men,&nbsp;Jinglu Zhang,&nbsp;Leilei Wang","doi":"10.1016/j.clim.2024.110268","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><p>To report a case of a five-month-old Chinese infant who died of interleukin-1 receptor-associated kinase-4 (IRAK-4) deficiency presenting with rapid and progressive <em>Pseudomonas aeruginosa</em> sepsis.</p></div><div><h3>Methods</h3><p>The genetic etiology of IRAK-4 deficiency was confirmed through trio-whole exome sequencing and Sanger sequencing. Functional consequences were invested using an in vitro minigene splicing assay.</p></div><div><h3>Results</h3><p>Trio-whole exome sequencing of genomic DNA identified two novel compound heterozygous mutations, <em>IRAK-4</em> (NM_016123.3): c.942–1G &gt; A and c.644_651+ 6delTTGCAGCAGTAAGT in the proband, which originated from his symptom-free parents. These mutations were predicted to cause frameshifts and generate three truncated proteins without enzyme activity.</p></div><div><h3>Conclusions</h3><p>Our findings expand the range of IRAK-4 mutations and provide functional support for the pathogenic effects of splice-site mutations. Additionally, this case highlights the importance of considering the underlying genetic defects of immunity when dealing with unusually overwhelming infections in previously healthy children and emphasizes the necessity for timely treatment with wide-spectrum antimicrobials.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Two novel compound heterozygous loss-of-function mutations cause fetal IRAK-4 deficiency presenting with Pseudomonas Aeruginosa sepsis\",\"authors\":\"Fang Zhang ,&nbsp;Zhiwei Wang ,&nbsp;Shuai Men,&nbsp;Jinglu Zhang,&nbsp;Leilei Wang\",\"doi\":\"10.1016/j.clim.2024.110268\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><p>To report a case of a five-month-old Chinese infant who died of interleukin-1 receptor-associated kinase-4 (IRAK-4) deficiency presenting with rapid and progressive <em>Pseudomonas aeruginosa</em> sepsis.</p></div><div><h3>Methods</h3><p>The genetic etiology of IRAK-4 deficiency was confirmed through trio-whole exome sequencing and Sanger sequencing. Functional consequences were invested using an in vitro minigene splicing assay.</p></div><div><h3>Results</h3><p>Trio-whole exome sequencing of genomic DNA identified two novel compound heterozygous mutations, <em>IRAK-4</em> (NM_016123.3): c.942–1G &gt; A and c.644_651+ 6delTTGCAGCAGTAAGT in the proband, which originated from his symptom-free parents. These mutations were predicted to cause frameshifts and generate three truncated proteins without enzyme activity.</p></div><div><h3>Conclusions</h3><p>Our findings expand the range of IRAK-4 mutations and provide functional support for the pathogenic effects of splice-site mutations. Additionally, this case highlights the importance of considering the underlying genetic defects of immunity when dealing with unusually overwhelming infections in previously healthy children and emphasizes the necessity for timely treatment with wide-spectrum antimicrobials.</p></div>\",\"PeriodicalId\":10392,\"journal\":{\"name\":\"Clinical immunology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-06-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1521661624003772\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1521661624003772","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

目的:报告一例五个月大的中国婴儿因白细胞介素-1受体相关激酶-4(IRAK-4)缺乏症而死亡的病例:方法:通过三重全外显子组测序和桑格测序确认了IRAK-4缺乏症的遗传学病因。方法:通过三全外显子组测序和桑格测序确认了 IRAK-4 缺乏症的遗传学病因,并使用体外微型基因剪接试验对其功能性后果进行了研究:结果:基因组DNA的三重全外显子测序发现了两个新的复合杂合突变,即IRAK-4 (NM_016123.3):c.942-1G > A和c.644_651+ 6delTTGCAGCAGTAAGT。据预测,这些突变会导致框架转换,并产生三个没有酶活性的截短蛋白:我们的研究结果扩大了IRAK-4突变的范围,并为剪接位点突变的致病作用提供了功能性支持。此外,本病例还强调了在处理以往健康儿童异常严重的感染时考虑潜在的免疫遗传缺陷的重要性,并强调了及时使用广谱抗微生物药物治疗的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Two novel compound heterozygous loss-of-function mutations cause fetal IRAK-4 deficiency presenting with Pseudomonas Aeruginosa sepsis

Purpose

To report a case of a five-month-old Chinese infant who died of interleukin-1 receptor-associated kinase-4 (IRAK-4) deficiency presenting with rapid and progressive Pseudomonas aeruginosa sepsis.

Methods

The genetic etiology of IRAK-4 deficiency was confirmed through trio-whole exome sequencing and Sanger sequencing. Functional consequences were invested using an in vitro minigene splicing assay.

Results

Trio-whole exome sequencing of genomic DNA identified two novel compound heterozygous mutations, IRAK-4 (NM_016123.3): c.942–1G > A and c.644_651+ 6delTTGCAGCAGTAAGT in the proband, which originated from his symptom-free parents. These mutations were predicted to cause frameshifts and generate three truncated proteins without enzyme activity.

Conclusions

Our findings expand the range of IRAK-4 mutations and provide functional support for the pathogenic effects of splice-site mutations. Additionally, this case highlights the importance of considering the underlying genetic defects of immunity when dealing with unusually overwhelming infections in previously healthy children and emphasizes the necessity for timely treatment with wide-spectrum antimicrobials.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Clinical immunology
Clinical immunology 医学-免疫学
CiteScore
12.30
自引率
1.20%
发文量
212
审稿时长
34 days
期刊介绍: Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.
期刊最新文献
Carrier frequency and incidence estimation of deficiency of adenosine deaminase 2 in the Chinese population based on massive exome sequencing data Editorial Board Corrigendum to "Immunomodulatory effect of Lactococcus lactis JCM5805 on human plasmacytoid dendritic cells" [Clinical Immunology 149/3PB (2013) 509-518]. Aberrant overexpression of the autoantigen protein vimentin promotes Th17 cell differentiation and autoimmune arthritis via activation of STAT3 signaling Characterization of primary Sjögren's syndrome in the Taiwan Han population through a genome-wide association study and polygenic risk score analysis
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1