Department of Pediatrics, Division of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Department of Pediatrics, Division of Rheumatology, Ankara Research and Training Hospital, University of Health Sciences, Ankara, Turkey.
Lupus. 2024 Aug;33(9):998-1003. doi: 10.1177/09612033241255011. Epub 2024 May 13.
We aimed to investigate the presence of monogenic causes of systemic lupus erythematosus (SLE) in our early-onset SLE patients.
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.
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 mutations [ and 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 mutation [ variant] had arthritis, nephritis, short stature, and skeletal dysplasia. Patient 4 with a heterozygote novel mutation [ variant] had skin findings and leukopenia. Patient 5 with novel variant [homozygous 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.
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.
我们旨在调查早发性系统性红斑狼疮（SLE）患者是否存在单基因病因。
本研究纳入了 15 例早发性（≤6 岁）儿童 SLE 患者。所有患者均符合系统性红斑狼疮国际合作临床（SLICC）标准。使用基因组 DNA 进行全外显子组测序（WES）。通过 Sanger 测序证实致病变异。
本研究纳入的 15 例早发性 SLE 患者的中位诊断年龄为 4（2-6）岁（F/M=12/3）。其中 5 例患者（33.3%）检测到显著基因突变。2 例患者（患者 1 和 2）存在纯合突变[和变体]，表现为皮肤受累和口腔溃疡。其中 1 例（患者 1）有关节炎和肾炎，另 1 例（患者 2）有非瘢痕性脱发和血小板减少症。目前他们均无临床活动，但血清学检查呈阳性。3 例患者（患者 3）存在纯合致病性突变[变体]，表现为关节炎、肾炎、身材矮小和骨骼发育不良。4 例患者（患者 4）为杂合新突变[变体]，表现为皮肤表现和白细胞减少症。5 例患者（患者 5）存在新变体[纯合变体]，表现为明显的皮肤表现、口腔溃疡、非瘢痕性脱发、全血细胞减少和总补体溶血 CH50 水平降低。所有患者经治疗后均有反应，且系统性红斑狼疮疾病活动指数（SLEDAI）评分较低。
早发性 SLE 应进行遗传病因调查，以更好地进行管理和遗传咨询。另一方面，多中心研究可能有助于进一步明确基因型-表型相关性。
