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EVALUATİON OF GENETİC TESTİNG İN ADULT PATİENTS WİTH SUSPECTED SYSTEMİC AUTOİNFLAMMATORY DİSORDERS

SİSTEMİK OTOİNFLAMATUAR HASTALIK ŞÜPHESİ OLAN ERİŞKİN HASTALARDA GENETİK TESTLERİN DEĞERLENDİRİLMESİ

Shirkhan Amikishiyev(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, RHEUMATOLOGY)1000-0000-2835-5017
Yildiz Akbal Engin(ISTANBUL BILIM UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, RHEUMATOLOGY)0000-0003-2066-822X
Tugba Kalayci(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF MEDICAL GENETICS)0000-0002-9963-5916
Lala Soltanova(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, GENERAL INTERNAL MEDICINE (MEDICINE))4000-0000-2442-0472
Yasemin Yalçınkaya(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, RHEUMATOLOGY)5000-0000-1935-7045
Bahar Artım Esen(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, RHEUMATOLOGY)6000-0000-2565-9395
Murat İnanç(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, RHEUMATOLOGY)7000-0000-2637-6558
Ayla Sahin(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF MEDICAL GENETICS)8000-0000-3049-1711
Aynur Aday(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF MEDICAL GENETICS)0000-0001-8072-0646
Sema Sırma Ekmekci(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF MEDICAL GENETICS)1000-0000-0212-0175
Neslihan Abacı(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF MEDICAL GENETICS)1100-0000-0299-6240
Şükrü Öztürk(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF MEDICAL GENETICS)1200-0000-0288-0974
Şükrü Palanduz(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF MEDICAL GENETICS)1300-0000-0294-3500
Ahmet Gül(ISTANBUL UNIVERSITY, İSTANBUL FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, RHEUMATOLOGY)1400-0000-0182-1937
Pages
70–81
Publication Date
2026-02-09
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

A better definition of those variant-negative patients may identify some subgroups of patients with SAID features associated with potential multifactorial causes or somatic mosaic variants.

📌 3 Key Takeaways

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Objective & Hypothesis:Objective: This study aimed to compare the clinical features of patients with suspected systemic autoinflammatory diseases (SAIDs) by genetic status to identify the characteristics of variant-negative patients.
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Key Findings & Data:Results: Records of 137 patients (79 females, 58 males, mean age 40.8±12.6) referred to our clinic between April 2019 and January 2023 were evaluated.
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Conclusion & Impact:A better definition of those variant-negative patients may identify some subgroups of patients with SAID features associated with potential multifactorial causes or somatic mosaic variants.
🔬Design:Review & Systematic Survey
📍Scope:2019 Verileri
⚙️Variables:Sistemik otoinflamatuar hastalıklar · genetik tarama · genetik varyant

Abstract

Objective: This study aimed to compare the clinical features of patients with suspected systemic autoinflammatory diseases (SAIDs) by genetic status to identify the characteristics of variant-negative patients. Materials and Methods: Clinical findings and results of the targeted next-generation sequencing of “fever panel genes” of patients with suspected SAIDs were retrospectively reviewed using their medical records. Results: Records of 137 patients (79 females, 58 males, mean age 40.8±12.6) referred to our clinic between April 2019 and January 2023 were evaluated. Variants associated with the relevant phenotypes were identified in 105 patients (76.6%), whereas 32 (23.4%) had no pathogenic or likely pathogenic variants, nor variants of uncertain significance (VUS). Variant-negative patients were older at diagnosis than variant-positive ones (38.2±13.6 vs. 28.4±14.8 years; p=0.02). Fever and arthritis occurred with a similar frequency between the groups. Compared with the variant-positive patients, the variant-negative group more often presented with nausea, weight loss, diarrhoea, erythema nodosum, headache, and sensorineural hearing loss (SNHL). Cerebrovascular occlusion occurred more frequently among variant-positive patients. Conclusion: Our study illustrates that the yield of genetic screening is expected to be low in patients older than 40 years and those presenting with nausea, weight loss, diarrhoea, erythema nodosum, headache, and SNHL. A better definition of those variant-negative patients may identify some subgroups of patients with SAID features associated with potential multifactorial causes or somatic mosaic variants.

Özet

Amaç: Bu çalışma, sistemik otoinflamatuvar hastalık (SOIH) şüphesi olan hastaların klinik özelliklerini genetik durumlarına göre karşılaştırarak varyant-negatif hastaların özelliklerini belirlemeyi amaçlamıştır. Gereç ve Yöntemler: SOIH şüphesiyle yollanan hastaların klinik bulguları ve ateş paneli genetik tarama sonuçları dosyalarındaki kayıtlardan retros-pektif olarak değerlendirildi. Bulgular: Kliniğimize Nisan 2019 ve Ocak 2023 tarihleri arasında başvuran toplam 137 hastanın (79 kadın, 58 erkek, ortalama yaş 40,8±12,6) verisi değerlendirildi. İlgili fenotiplerle ilişkili varyantlar 105 hastada (%76,6) saptanırken, 32 hastada (%23,4) patojenik, olası patojenik veya anlamı belirsiz varyant (VUS) tespit edilmedi. Varyant-negatif hastalar, varyant-pozitif hastalara kıyasla tanı anında daha ileri yaştaydı (38,2±13,6 yıla karşı 28,4±14,8; p=0,02). Ateş ve artrit her iki grupta benzer sıklıkta görüldü. Varyant-negatif grupta bulantı, kilo kaybı, ishal, eritema nodozum, baş ağrısı ve sensörinöral işitme kaybı (SNIK) daha sık izlendi. Serebrovasküler oklüzyon ise varyant-pozitif hastalarda daha sık görüldü. Sonuç: Bu araştırma, 40 yaşının üstünde ve bulantı, kilo kaybı, ishal, eritema nodozum, başağrısı ve SNIK bulguları olan hastalarda genetik taramada sonuç elde etme oranının düşük olduğunu göstermektedir. Varyant saptanmayan hastaların özelliklerinin daha iyi tanımlanması sonucu multifaktöriyel ya da somatik mozaisizmle ilişkili SOIH alt grup-larının saptanması mümkün olabilir.

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Cite This Article

Amikishiyev, S., Engin, Y. A., Kalayci, T., Soltanova, L., Yalçınkaya, Y., Esen, B. A., İnanç, M., Sahin, A., Aday, A., Ekmekci, S. S., Abacı, N., Öztürk, Ş., Palanduz, Ş., Gül, A. (2026). EVALUATİON OF GENETİC TESTİNG İN ADULT PATİENTS WİTH SUSPECTED SYSTEMİC AUTOİNFLAMMATORY DİSORDERS. İstanbul Tıp Fakültesi Dergisi, Cilt: 89 Sayı: 1, 70–81. https://doi.org/10.26650/IUITFD.1717786

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