Detection of genetic mutations underlying early-onset systemic lupus erythematosus.

IF 1.9 4区 医学 Q3 RHEUMATOLOGY
Lupus Pub Date : 2024-08-01 Epub Date: 2024-05-13 DOI:10.1177/09612033241255011
Seher Sener, Erdal Sag, Xu Han, Yelda Bilginer, Qing Zhou, Seza Ozen
{"title":"Detection of genetic mutations underlying early-onset systemic lupus erythematosus.","authors":"Seher Sener, Erdal Sag, Xu Han, Yelda Bilginer, Qing Zhou, Seza Ozen","doi":"10.1177/09612033241255011","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>We aimed to investigate the presence of monogenic causes of systemic lupus erythematosus (SLE) in our early-onset SLE patients.</p><p><strong>Methods: </strong>Fifteen pediatric SLE cases who had early disease onset (≤6 years) were enrolled in this study. All patients fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) criteria. Genomic DNA was used for whole exome sequencing (WES). Pathogenic variants were confirmed by Sanger sequencing.</p><p><strong>Results: </strong>The median age at diagnosis of 15 early-onset SLE patients included in the study was 4 (2-6) years (F/M = 12/3). Significant gene mutations were detected in five of these patients (33.3%). Patients 1 and 2 with homozygous <i>DNASE1L3</i> mutations [<i>c.320+4_320+7del</i> and <i>G188 A (c.563 G>C)</i> variants] had skin involvement and oral ulcers. One of them (patient 1) had arthritis and nephritis, and another (patient 2) had nonscarring alopecia and thrombocytopenia. They are currently clinically inactive but have positive serological findings. Patient 3 with homozygous pathogenic <i>ACP5</i> mutation [<i>G109 R (c.325 G>A)</i> variant] had arthritis, nephritis, short stature, and skeletal dysplasia. Patient 4 with a heterozygote novel <i>IFIH1</i> mutation [<i>L809 F (c.2425 C>T)</i> variant] had skin findings and leukopenia. Patient 5 with novel <i>C1S</i> variant [homozygous <i>C147 W (c.441 C>G)</i> variant] had marked skin findings, oral ulcers, nonscarring alopecia, pancytopenia, and low total hemolytic complement CH50 level. All patients have responded to the treatments and have low Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, on therapy.</p><p><strong>Conclusion: </strong>Genetic causes should be investigated in early-onset SLE, for better management and genetic counseling. On the other hand, multicenter studies may help to further define genotype-phenotype associations.</p>","PeriodicalId":18044,"journal":{"name":"Lupus","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lupus","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/09612033241255011","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/13 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Objective: We aimed to investigate the presence of monogenic causes of systemic lupus erythematosus (SLE) in our early-onset SLE patients.

Methods: Fifteen pediatric SLE cases who had early disease onset (≤6 years) were enrolled in this study. All patients fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) criteria. Genomic DNA was used for whole exome sequencing (WES). Pathogenic variants were confirmed by Sanger sequencing.

Results: The median age at diagnosis of 15 early-onset SLE patients included in the study was 4 (2-6) years (F/M = 12/3). Significant gene mutations were detected in five of these patients (33.3%). Patients 1 and 2 with homozygous DNASE1L3 mutations [c.320+4_320+7del and G188 A (c.563 G>C) variants] had skin involvement and oral ulcers. One of them (patient 1) had arthritis and nephritis, and another (patient 2) had nonscarring alopecia and thrombocytopenia. They are currently clinically inactive but have positive serological findings. Patient 3 with homozygous pathogenic ACP5 mutation [G109 R (c.325 G>A) variant] had arthritis, nephritis, short stature, and skeletal dysplasia. Patient 4 with a heterozygote novel IFIH1 mutation [L809 F (c.2425 C>T) variant] had skin findings and leukopenia. Patient 5 with novel C1S variant [homozygous C147 W (c.441 C>G) variant] had marked skin findings, oral ulcers, nonscarring alopecia, pancytopenia, and low total hemolytic complement CH50 level. All patients have responded to the treatments and have low Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, on therapy.

Conclusion: Genetic causes should be investigated in early-onset SLE, for better management and genetic counseling. On the other hand, multicenter studies may help to further define genotype-phenotype associations.

检测早发型系统性红斑狼疮的基因突变。
目的:我们旨在研究早发型系统性红斑狼疮(SLE)患者中是否存在单基因病因:我们旨在研究早期发病的系统性红斑狼疮(SLE)患者中是否存在单基因病因:本研究共纳入了15例早期发病(≤6岁)的小儿系统性红斑狼疮患者。所有患者均符合系统性红斑狼疮国际合作诊所(SLICC)的标准。基因组DNA用于全外显子组测序(WES)。结果:结果:参与研究的15名早发系统性红斑狼疮患者确诊时的中位年龄为4(2-6)岁(女/男=12/3)。其中5名患者(33.3%)检测到了明显的基因突变。1号和2号患者的同源DNASE1L3基因突变[c.320+4_320+7del和G188 A (c.563 G>C)变异]累及皮肤和口腔溃疡。其中一人(患者 1)患有关节炎和肾炎,另一人(患者 2)患有非瘢痕性脱发和血小板减少症。他们目前没有临床症状,但血清学检查结果呈阳性。患者 3 患有同型致病性 ACP5 突变[G109 R (c.325 G>A) 变异],患有关节炎、肾炎、身材矮小和骨骼发育不良。患者 4 患有杂合子新型 IFIH1 突变[L809 F (c.2425 C>T) 变异],有皮肤病和白细胞减少症。患者 5 患有新型 C1S 变异[同型 C147 W (c.441 C>G) 变异],有明显的皮肤症状、口腔溃疡、非瘢痕性脱发、全血细胞减少和低总溶血补体 CH50 水平。所有患者都对治疗有反应,并且在治疗过程中系统性红斑狼疮疾病活动指数(SLEDAI)评分较低:结论:应研究早发性系统性红斑狼疮的遗传原因,以便进行更好的治疗和遗传咨询。另一方面,多中心研究可能有助于进一步确定基因型与表型之间的关系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Lupus
Lupus 医学-风湿病学
CiteScore
4.20
自引率
11.50%
发文量
225
审稿时长
1 months
期刊介绍: The only fully peer reviewed international journal devoted exclusively to lupus (and related disease) research. Lupus includes the most promising new clinical and laboratory-based studies from leading specialists in all lupus-related disciplines. Invaluable reading, with extended coverage, lupus-related disciplines include: Rheumatology, Dermatology, Immunology, Obstetrics, Psychiatry and Cardiovascular Research…
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信