med records Medical Records 2687-4555 Tıbbi Kayıtlar Derneği Gene Expression Gen İfadesi SLE'nin Genetik Karmaşıklığı: Gen Mutasyonlarının ve Klinik Korelasyonların Retrospektif Analizi Genetic Complexity of SLE: A Retrospective Analysis of Gene Mutations and Clinical Correlations https://orcid.org/0000-0001-7118-7958 Eser Metin SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, İSTANBUL ÜMRANİYE SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ https://orcid.org/0000-0002-5027-6756 Hekimoğlu Gulam SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, HAMİDİYE ULUSLARARASI TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, HİSTOLOJİ VE EMBRİYOLOJİ ANABİLİM DALI https://orcid.org/0000-0002-1125-7720 Kasapçopur Özgür İSTANBUL ÜNİVERSİTESİ, CERRAHPAŞA TIP FAKÜLTESİ https://orcid.org/0000-0002-5365-3457 Şahin Sezgin İSTANBUL ÜNİVERSİTESİ, CERRAHPAŞA TIP FAKÜLTESİ https://orcid.org/0000-0002-1135-7720 Akay Nergis İSTANBUL ÜNİVERSİTESİ, CERRAHPAŞA TIP FAKÜLTESİ https://orcid.org/0000-0002-5079-5644 Sözeri Betül SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, İSTANBUL ÜMRANİYE SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ 03 22 2026 0 1 08 17 2025 01 12 2026 Copyright © 2019, Medical Records 2019 Medical Records

Amaç: Sistemik lupus eritematozus (SLE), otoantikor ve immün kompleks üretimi ile karakterize multisistemik bir otoimmün hastalıktır. Bu çalışma, spesifik gen mutasyonlarını klinik bulgularla ilişkilendirerek SLE patogenezini aydınlatmayı amaçlamaktadır.Gereç ve Yöntem: Bu retrospektif çalışmada, 19 SLE hastasının periferik kanındaki gen mutasyonları yeni nesil dizileme kullanılarak analiz edildi.Bulgular: Her gen mutasyonu için mutasyon oranı ve ilişkili klinik semptomlar incelendi. SLE hastalarında %42'lik bir mutasyon oranı tespit edildi. Çalışma, SLE'nin birden fazla gen mutasyonu ile ilişkili olduğunu ve bunun karmaşık klinik tablosuna katkıda bulunduğunu buldu. Spesifik gen mutasyonları, glomerülonefrit ve poliartrit gibi farklı klinik semptomlarla ilişkiliydi ve SOCS1 mutasyonlarıyla ilişkiliydi. Skolyoz, STAT1 mutasyonlarıyla ilişkiliydi. Işığa duyarlı malar döküntüsü, kompleman mutasyonlarıyla (C1qB, C1qC ve C3) bağlantılıydı. Eritematöz malar döküntüsü, PTPN22 mutasyonlarıyla ilişkiliydi. Ayrıca, artraljiler TREX1 mutasyonlarıyla ilişkiliydi.Sonuç: SLE, farklı gen mutasyonlarından kaynaklanan semptom çeşitliliğine sahip, çok yönlü, multisistem bir otoimmün hastalıktır. Çalışma, klinik semptomlara dayanarak gen mutasyonlarını tahmin ederek ve bu mutasyonları moleküler testlerle doğrulayarak hastaya özgü gen tedavisini savunmaktadır.

Aim: To investigate the genetic basis of systemic lupus erythematosus (SLE) by identifying pathogenic gene variants and examining their associations with distinct clinical and phenotypic manifestations, to improve understanding of disease heterogeneity and support the development of personalized therapeutic approaches.Material and Methods: In this retrospective study, gene mutations in the peripheral blood of 19 SLE patients were analyzed using next-generation sequencing. Results: The mutation rate and associated clinical symptoms for each gene mutation were observed. A mutation rate of 42% was discovered among the SLE patients. The study found that SLE is associated with multiple gene mutations, contributing to its complex clinical presentation. Specific gene mutations were associated with distinct clinical symptoms, such as glomerulonephritis and polyarthritis were linked to SOCS1 mutations. Scoliosis was associated with STAT1 mutations. A photosensitive malar rash was connected to complement mutations (C1qB, C1qC, and C3). An erythematous malar rash was related to PTPN22 mutations. Additionally, arthralgias were associated with TREX1 mutations.Conclusion: SLE is a multifaceted, multisystem autoimmune disease with symptom variability from different gene mutations. The study advocates patient-specific gene therapy by predicting gene mutations based on clinical symptoms and confirming these mutations through molecular tests.

 Glomerulonephritis Arthritis SOCS1 STAT1 PTPN22 Complement mutations Glomerülonefrit Artrit SOCS1 STAT1 PTPN22 Kompleman mutasyonları Ahmad YA, Bruce IN. Genetic epidemiology: systemic lupus erythematosus. Arthritis Res. 2001;3:331-6. Yoshimura A, Naka T, Kubo M. SOCS proteins, cytokine signaling and immune regulation. Nat Rev Immunol. 2007;7:454-65. Couto AR, Bruges-Armas J, Peach CA, et al. A novel LEMD3 mutation common to patients with osteopoikilosis with and without melorheostosis. Calcif Tissue Int. 2007;81:81-4. Ott N, Faletti L, Heeg M, Andreani V, Grimbacher B. JAKs and STATs from a Clinical Perspective: Loss-of-Function Mutations, Gain-of-Function Mutations, and Their Multidimensional Consequences. J Clin Immunol. 2023;43:1326-59. Rauch I, Müller M, Decker T. The regulation of inflammation by interferons and their STATs. JAKSTAT. 2013;2:e23820. Botto M, Kirschfink M, Macor P, et al. Complement in human diseases: Lessons from complement deficiencies. Mol Immunol. 2009;46:2774-83. Pickering MC, Walport MJ. Links between complement abnormalities and systemic lupus erythematosus. Rheumatology (Oxford). 2000;39:133-41. Walport MJ. Complement and systemic lupus erythematosus. Arthritis Res. 2002;4 Suppl 3:S279-S93. Liu T, Yang M, Xia Y, et al. Microarray-based analysis of renal complement components reveals a therapeutic target for lupus nephritis. Arthritis Res Ther. 2021;23:223. Truedsson L, Bengtsson AA, Sturfelt G. Complement deficiencies and systemic lupus erythematosus. Autoimmunity. 2007;40:560-6. Namjou B, Kim-Howard X, Sun C, et al. PTPN22 association in systemic lupus erythematosus (SLE) with respect to individual ancestry and clinical sub-phenotypes. PLoS One. 2013;8:e69404. Mumm S, Wenkert D, Zhang X, McAlister WH, Mier RJ, Whyte MP. Deactivating germline mutations in LEMD3 cause osteopoikilosis and Buschke-Ollendorff syndrome, but not sporadic melorheostosis. J Bone Miner Res. 2007;22:243-50. Hellemans J, Preobrazhenska O, Willaert A, et al. Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome, and melorheostosis. Nat Genet. 2004;36:1213-18. Crow YJ, Hayward BE, Parmar R, et al. Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus. Nat Genet. 2006;38:917-20. Rice GI, Bond J, Asipu A, et al. Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as a regulator of the innate immune response. Nat Genet. 2009;41:829-32. Ensembl VEP pick options. https://www.ensembl.org/info/docs/tools/vep/script/vep_other.html#pick_options Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), ncbi.nlm.nih.gov/clinvar/submitters/505954/ Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), ncbi.nlm.nih.gov/clinvar/submitters/504863/ Pharmacogenomics Knowledge Base,Stanford University (PharmGKB), ncbi.nlm.nih.gov/clinvar/submitters/500295/ The Clinical and Functional TRanslation of CFTR (CFTR2), ncbi.nlm.nih.gov/clinvar/submitters/500092/ ClinGen RASopathy Expert Panel (ClINGEN-RAS), ncbi.nlm.nih.gov/clinvar/submitters/506439/ ClinGen Inherited Cardiomyopathy Expert Panel (CMP-EP), ncbi.nlm.nih.gov/clinvar/submitters/506161/ Maxwell KN, Hart SN, Vijai J, et al. Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer. Am J Hum Genet. 2016;98:801-17. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405-24. Fujimoto M, Tsutsui H, Xinshou O, et al. Inadequate induction of suppressor of cytokine signaling-1 causes systemic autoimmune diseases. Int Immunol. 2004;16:303-14. Egan PJ, Lawlor KE, Alexander WS, Wicks IP. Suppressor of cytokine signaling-1 regulates acute inflammatory arthritis and T cell activation. J Clin Invest. 2003;111:915-24. Shumilova A, Vital EM. Musculoskeletal manifestations of systemic lupus erythematosus. Best Pract Res Clin Rheumatol. 2023;37:101859. Graham RR, Cotsapas C, Davies L, et al. Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat Genet. 2008;40:1059-61. Gregersen PK, Olsson LM. Recent advances in the genetics of autoimmune disease. Annu Rev Immunol. 2009;27:363-91. Bottini N, Peterson EJ. Tyrosine phosphatase PTPN22: multifunctional regulator of immune signaling, development, and disease. Annu Rev Immunol. 2014;32:83-119. Wordsworth P, Chan M. Melorheostosis and Osteopoikilosis: A Review of Clinical Features and Pathogenesis. Calcif Tissue Int. 2019;104:530-43. Lee-Kirsch MA, Chowdhury D, Harvey S, et al. A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus. J Mol Med (Berl). 2007;85:531-7. Lee-Kirsch MA, Günther C, Roers A. Nucleic acid-mediated autoinflammation and autoimmunity-type I interferonopathies. J Mol Med (Berl). 2016;94:1081-4. Parks CG, de Souza Espindola Santos A, Barbhaiya M, Costenbader KH. Understanding the role of environmental factors in the development of systemic lupus erythematosus. Best Pract Res Clin Rheumatol. 2017;31:306-20.