Predicting homozygous M694V genotype in paediatric FMF: multicentre analysis and scoring system proposal.
| Title: | Predicting homozygous M694V genotype in paediatric FMF: multicentre analysis and scoring system proposal. |
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| Authors: | Tunce E; Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Training and Research Hospital, İstanbul, Türkiye.; Atamyıldız Uçar S; Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Training and Research Hospital, İstanbul, Türkiye.; Polat MC; Department of Pediatric Rheumatology, University of Health Sciences, Ankara Bilkent City Hospital, Ankara, Türkiye.; Altuğ Gücenmez Ö; Department of Pediatric Rheumatology, University of Health Sciences, Dr. Behçet Uz Pediatric Diseases and Surgery Training and Research Hospital, İzmir, Türkiye.; Çakan M; Department of Pediatric Rheumatology, University of Health Sciences, Zeynep Kamil Women and Children's Diseases Training and Research Hospital, İstanbul, Türkiye.; Bozkaya Yücel B; Department of Pediatric Rheumatology, University of Health Sciences, Samsun Training and Research Hospital, Samsun, Türkiye.; Arslanoğlu Aydın E; Department of Pediatric Rheumatology, Ankara Etlik City Hospital, Ankara, Türkiye.; Doğan Kuzuca T; Department of Pediatric Rheumatology, Eskisehir Osmangazi University Faculty of Medicine, Eskişehir, Türkiye.; Kılıç Könte E; Department of Pediatric Rheumatology, İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, İstanbul, Türkiye.; Demirhan S; Department of Pediatrics, University of Health Sciences, Kayseri City Hospital, Kayseri, Türkiye.; Küçük E; Department of Pediatric Rheumatology, İstanbul Medeniyet University Faculty of Medicine, İstanbul, Türkiye.; Arık SD; Department of Pediatric Rheumatology, İstanbul University Faculty of Medicine, İstanbul, Türkiye.; Vatansever G; Department of Pediatric Rheumatology, Uludağ University Faculty of Medicine, Bursa, Türkiye.; Özkaya O; Department of Pediatric Rheumatology, İstinye University Faculty of Medicine, İstanbul, Türkiye.; Tekcan D; Department of Pediatric Nephrology, Ondokuz Mayıs University Faculty of Medicine, Samsun, Türkiye.; Nalçacıoğlu H; Department of Pediatric Nephrology, Ondokuz Mayıs University Faculty of Medicine, Samsun, Türkiye.; Tanatar A; Department of Pediatric Rheumatology, Gaziantep City Hospital, Gaziantep, Türkiye.; Karakaş HD; Department of Pediatric Rheumatology, Diyarbakır Children's Hospital, Diyarbakır, Türkiye.; Açarı C; Department of Pediatric Rheumatology, İnönü University Faculty of Medicine, Malatya, Türkiye.; Doğantan Ş; Department of Pediatric Rheumatology, Mersin City Hospital, Mersin, Türkiye.; Şener S; Department of Pediatric Rheumatology, Adana City Research and Training Hospital, Adana, Türkiye.; Kışla Ekinci RM; Department of Pediatric Rheumatology, Çukurova University Faculty of Medicine, Adana, Türkiye.; Garipçin P; Department of Pediatric Rheumatology, Erciyes University Faculty of Medicine, Kayseri, Türkiye.; Ercan Emreol H; Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Türkiye.; Kurt T; Department of Pediatric Rheumatology, University of Health Sciences, Bursa City Hospital, Bursa, Türkiye.; Adıgüzel Dündar H; Department of Pediatric Rheumatology, University of Health Sciences, Dr. Behçet Uz Pediatric Diseases and Surgery Training and Research Hospital, İzmir, Türkiye.; Girgeç A; Department of Pediatric Rheumatology, Gaziantep University Faculty of Medicine, Gaziantep, Türkiye.; Arif Tutuş A; Department of Pediatric Rheumatology, Marmara University Faculty of Medicine, İstanbul, Türkiye.; Köker O; Department of Pediatric Rheumatology, Marmara University Faculty of Medicine, İstanbul, Türkiye.; Cevizbaş S; Department of Pediatric Rheumatology, Dokuz Eylül University Faculty of Medicine, İzmir, Türkiye.; Kutlar Tanıdır M; Department of Pediatric Rheumatology, Gazi University Faculty of Medicine, Ankara, Türkiye.; Tığrak SN; Department of Pediatric Rheumatology, Pamukkale University Faculty of Medicine, Denizli, Türkiye.; Sezer M; Department of Pediatric Rheumatology, Ankara Training and Research Hospital, Ankara, Türkiye.; Kazanasmaz H; Department of Pediatric Rheumatology, Karadeniz Technical University Faculty of Medicine, Trabzon, Türkiye.; Öksel B; Department of Pediatric Rheumatology, Kocaeli University Faculty of Medicine, Kocaeli, Türkiye.; Taşkın RB; Department of Pediatric Rheumatology, Ege University Faculty of Medicine, İzmir, Türkiye.; Gümüşsoy Ay E; Department of Pediatric Rheumatology, Fırat University Faculty of Medicine, Elazığ, Türkiye.; Coşkuner T; Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Training and Research Hospital, İstanbul, Türkiye.; Özomay Baykal G; Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Training and Research Hospital, İstanbul, Türkiye.; Yiğit RE; Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Training and Research Hospital, İstanbul, Türkiye.; Türkmen Ş; Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Training and Research Hospital, İstanbul, Türkiye.; Ulu K; Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Training and Research Hospital, İstanbul, Türkiye.; Taşkın SN; Department of Pediatric Rheumatology, Eskişehir City Hospital, Eskişehir, Türkiye.; Otar Yener G; Department of Pediatric Rheumatology, Eskişehir City Hospital, Eskişehir, Türkiye.; Demir F; Department of Pediatric Rheumatology, Acıbadem Ataşehir Hospital, Istanbul, Türkiye.; Kilic SS; Department of Pediatric Rheumatology, Uludağ University Faculty of Medicine, Bursa, Türkiye.; Gürgöze MK; Department of Pediatric Rheumatology, Fırat University Faculty of Medicine, Elazığ, Türkiye.; Aksu G; Department of Pediatric Rheumatology, Ege University Faculty of Medicine, İzmir, Türkiye.; Sönmez HE; Department of Pediatric Rheumatology, Kocaeli University Faculty of Medicine, Kocaeli, Türkiye.; Türkuçar S; Department of Pediatric Rheumatology, Pamukkale University Faculty of Medicine, Denizli, Türkiye.; Kalyoncu M; Department of Pediatric Rheumatology, Karadeniz Technical University Faculty of Medicine, Trabzon, Türkiye.; Bakkaloğlu S; Department of Pediatric Rheumatology, Gazi University Faculty of Medicine, Ankara, Türkiye.; Özkayın N; Department of Pediatric Nephrology, Trakya University Faculty of Medicine, Edirne, Türkiye.; Kasap Demir B; Department of Pediatric Nephrology and Rheumatology, İzmir Katip Çelebi University Faculty of Medicine, Izmir, Türkiye.; Ünsal E; Department of Pediatric Rheumatology, Dokuz Eylül University Faculty of Medicine, İzmir, Türkiye.; Yüksel S; Department of Pediatric Nephrology and Rheumatology, University of Çanakkale Onsekiz Mart Faculty of Medicine, Çanakkale, Türkiye.; Balat A; Department of Pediatric Rheumatology, Gaziantep University Faculty of Medicine, Gaziantep, Türkiye.; Bilginer Y; Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Türkiye.; Paç Kısaarslan A; Department of Pediatric Rheumatology, Erciyes University Faculty of Medicine, Kayseri, Türkiye.; Dönmez O; Department of Pediatric Nephrology and Rheumatology, Uludağ University Faculty of Medicine, Bursa, Türkiye.; Aktay Ayaz N; Department of Pediatric Rheumatology, İstanbul University Faculty of Medicine, İstanbul, Türkiye.; Öztürk K; Department of Pediatric Rheumatology, İstanbul Medeniyet University Faculty of Medicine, İstanbul, Türkiye.; Demir S; Department of Pediatric Rheumatology, Eskisehir Osmangazi University Faculty of Medicine, Eskişehir, Türkiye.; Bağlan E; Department of Pediatric Rheumatology, Ankara Etlik City Hospital, Ankara, Türkiye.; Çelikel E; Department of Pediatric Rheumatology, University of Health Sciences, Ankara Bilkent City Hospital, Ankara, Türkiye.; Kasapçopur Ö; Department of Pediatric Rheumatology, İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, İstanbul, Türkiye.; Özen S; Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Türkiye.; Sözeri B; Department of Pediatric Rheumatology, University of Health Sciences, Ümraniye Training and Research Hospital, İstanbul, Türkiye. |
| Source: | Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2025 Aug 01; Vol. 64 (8), pp. 4816-4824. |
| Publication Type: | Journal Article; Multicenter Study |
| Language: | English |
| Journal Info: | Publisher: Oxford University Press Country of Publication: England NLM ID: 100883501 Publication Model: Print Cited Medium: Internet ISSN: 1462-0332 (Electronic) Linking ISSN: 14620324 NLM ISO Abbreviation: Rheumatology (Oxford) Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Oxford, UK : Avenel, N.J. : Oxford University Press ; Distributed by Mercury International, c1999- |
| MeSH Terms: | Familial Mediterranean Fever*/genetics ; Familial Mediterranean Fever*/diagnosis ; Familial Mediterranean Fever*/epidemiology ; Familial Mediterranean Fever*/drug therapy ; Pyrin*/genetics; Turkey/epidemiology ; Colchicine/therapeutic use ; Humans ; Male ; Female ; Cross-Sectional Studies ; Child, Preschool ; Child ; Genotype ; Homozygote ; Adolescent |
| Abstract: | Objectives: This study aimed to evaluate the predictability of the homozygous M694V genotype in paediatric FMF patients and to develop a clinical scoring system to enhance disease management strategies.; Methods: This nationwide, multicentre, cross-sectional study included 3981 paediatric FMF patients with biallelic pathogenic variants in exon 10 of the Mediterranean fever gene. Patients were divided into two groups: group 1 (homozygous M694V) and group 2 (other variants). Data were collected from 37 paediatric rheumatology and/or nephrology clinics across Türkiye, covering patients followed between 2014 and 2023.; Results: Group 1 had significantly earlier symptom onset (≤3 years: 49.8% vs 43.9%, P < 0.001) and diagnosis (median age: 5 years vs 5.8 years, P < 0.001) compared with group 2. A higher prevalence of family history of FMF was observed in group 1 (P < 0.001). Clinical manifestations, including arthritis (27.5%), erysipelas-like erythema (ELE) (20.3%) and protracted febrile myalgia syndrome (PFMS) (3.6%), were significantly more frequent in group 1 (P < 0.001 for all). Colchicine resistance was also higher in group 1 (18.1% vs 5.1%, P < 0.001). Logistic regression analysis showed that ≤3 years of age at symptom onset, family history, arthritis, myalgia, PFMS, ELE and splenomegaly were independent predictors of the homozygous M694V genotype. A clinical scoring system was proposed based on these findings.; Conclusion: This study provides valuable insights into the clinical predictors of the homozygous M694V genotype in paediatric FMF. The proposed scoring system will support clinicians in prognosis assessment and treatment planning, contributing to improved patient outcomes.; (© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.) |
| Contributed Indexing: | Keywords: FMF; M694V; genotype; paediatric; phenotype; predictability; scoring system |
| Substance Nomenclature: | 0 (Pyrin); 0 (MEFV protein, human); SML2Y3J35T (Colchicine) |
| Entry Date(s): | Date Created: 20250421 Date Completed: 20250801 Latest Revision: 20250806 |
| Update Code: | 20260130 |
| DOI: | 10.1093/rheumatology/keaf221 |
| PMID: | 40257440 |
| Database: | MEDLINE |
Journal Article; Multicenter Study