{"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.
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…