Aljaberi Najla, Bharathan Anjali, Gopal Remya Prajesh, Mohammed Ekhlass, Al Shibli Fatema, Tabouni Mohammed, Alhmoudi Sara, Kizhakkedath Praseetha, Baydoun Ibrahim, Allam Mushal, Mustafa Noor, Aljasmi Fatma, Al Dhaheri Afra, Alblooshi Hiba
Department of Pediatrics, United Arab Emirates University College of Medicine and Health Sciences, Al Ain, Abu Dhabi, UAE.
Department of Genetics and Genomics, United Arab Emirates University College of Medicine and Health Sciences, Al Ain, Abu Dhabi, UAE.
Lupus Sci Med. 2025 Feb 13;12(1):e001477. doi: 10.1136/lupus-2024-001477.
To evaluate the functional impact of a novel variant (c.572A>G, p.Asn191Ser) in three families with SLE and hypocomplementaemic urticarial vasculitis (HUV) from the United Arab Emirates.
Whole-exome sequencing was performed on affected patients and findings were confirmed using Sanger sequencing in family members. DNASE1L3 protein expression, secretion and enzymatic activity were assessed in HEK293 cell lines. Plasma smear assay for neutrophil extracellular traps (NETs) was evaluated in patients, family members and healthy control.
A total of seven patients diagnosed with both SLE and HUV were identified from three unrelated families. All affected individuals were found to carry a homozygous c.572A>G, p.Asn191Ser (191S) variant in . The variant 191S was shown to impact the secretion and activity of DNASE1L3. Patients homozygous for 191S variant had significantly higher burden (p=0.0409) of NET structure in comparison to heterozygous and healthy control.
We functionally evaluated the effect of a novel (c.572A>G, p.Asn191Ser) in familial SLE with a consistent pattern of HUV across seven patients. This variant resulted in impaired secretion and enzymatic activity of DNASE1L3 along with increased NETosis in patients with homozygous genotype.
评估一种新型变体（c.572A>G，p.Asn191Ser）对来自阿拉伯联合酋长国的三个系统性红斑狼疮（SLE）合并低补体血症性荨麻疹性血管炎（HUV）家庭的功能影响。
对受影响的患者进行全外显子测序，并使用桑格测序法在家庭成员中进行验证。在HEK293细胞系中评估DNASE1L3蛋白的表达、分泌和酶活性。对患者、家庭成员和健康对照进行中性粒细胞胞外陷阱（NETs）的血浆涂片检测。
从三个无血缘关系的家庭中总共鉴定出7名诊断为SLE和HUV的患者。所有受影响个体均被发现携带纯合的c.572A>G，p.Asn191Ser（191S）变体。结果显示，191S变体影响DNASE1L3的分泌和活性。与杂合子和健康对照相比，191S变体纯合子患者的NET结构负担显著更高（p=0.0409）。
我们对一种新型变体（c.572A>G，p.Asn191Ser）在家族性SLE中的作用进行了功能评估，该变体在7名患者中呈现出一致的HUV模式。这种变体导致DNASE1L3的分泌和酶活性受损，同时纯合基因型患者的NETosis增加。
