Is there any difference between M694V heterozygote and non-exon 10 mutations on symptoms onset and response to colchicine treatment?

Year 2024, Volume: 17 Issue: 3, 550 - 559, 05.07.2024

Hatice Adıgüzel Dundar , Serkan Türkuçar , Ceyhun Açarı , Özge Altuğ Gücenmez , Balahan Makay , Erbil Ünsal

https://doi.org/10.31362/patd.1496674

Abstract

Purpose: Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory syndrome throughout the world. The most frequent genotype-phenotype correlation is in a certain part of exon 10, especially M694V mutation. There are also a group of patients with non-exon 10 mutations, who have a similar clinical spectrum of the disease. We aim to investigate the genotype-phenotype differences between M694V heterozygote mutations and non-exon 10 mutations.
Materials and methods: Data charts of children (n=431) with FMF from two tertiary hospitals were reviewed. Patients were divided into two groups with regard to having M694V heterozygote or non-exon 10 mutations. Genotype-phenotype features and response to treatment were compared.
Results: There were M694V heterozygote mutations in 128 (29.7%) patients and non-exon 10 mutations in 303 (70.3%) patients. The follow-up period was 54.5 (33-105) months. There was no difference between the age of symptoms onset, the age of diagnosis, and the diagnosis delay time. The family history in patients with M694V heterozygote mutation was statistically positive compared to non-exon 10 mutation group (p=0.001). The symptoms of joint involvement as arthritis and PRAS scores were significantly higher in the M694V heterozygote group (p=0.026 and p=0.001). Additionally, biological agent need due to colchicine unresponsiveness was statistically higher in M694V heterozygote group than group with non-exon 10 mutation (p=0.004).
Conclusion: There is a significant difference between children with M694V and non-exon 10 mutations, even when the M694V mutation is present in one allele only. Family history with FMF, musculoskeletal symptoms, and unresponsiveness to colchicine are main parameters.

Keywords

Familial Mediterranean Fever, M694V, MEFV mutation, colchicine

M694V heterozigot ve non-ekzon 10 mutasyonları arasında semptomların başlangıcı ve kolşisin tedavisine yanıt açısından fark var mıdır?

Abstract

Amaç: Ailesel Akdeniz Ateşi (AAA), tüm dünyada en sık görülen kalıtsal otoinflamatuvar sendromdur. En sık genotip-fenotip korelasyonu ekzon 10'un belirli bir kısmında, özellikle M694V mutasyonundadır. Ekzon 10 mutasyonu olmayan ve benzer klinik spektruma sahip bir grup hasta da bulunmaktadır. Amacımız M694V heterozigot mutasyonları ve ekzon 10 dışı mutasyonlar arasındaki genotip-fenotip farklılıklarını araştırmaktır.
Gereç ve yöntem: İki üçüncü basamak hastaneden AAA'lı çocukların (n=431) veri dosyaları incelendi. Hastalar M694V heterozigot veya non-ekson 10 mutasyonuna sahip olma açısından iki gruba ayrıldı. Genotip-fenotip özellikleri ve tedaviye yanıt karşılaştırıldı.
Bulgular: 128 (%29,7) hastada M694V heterozigot mutasyonu ve 303 (%70,3) hastada non-ekson 10 mutasyonu vardı. Takip süresi 54,5 (33-105) aydı. Semptomların başlama yaşı, tanı yaşı ve tanı gecikme süresi arasında fark yoktu. M694V heterozigot mutasyonu olan hastalarda aile öyküsü, ekzon 10 mutasyonu olmayan gruba kıyasla istatistiksel olarak pozitifti (p=0,001). Artrit olarak eklem tutulumu semptomları ve PRAS skorları M694V heterozigot grubunda anlamlı olarak daha yüksekti (p=0,026 ve p=0,001). Ayrıca, kolşisin yanıtsızlığı nedeniyle biyolojik ajan ihtiyacı M694V heterozigot grupta ekzon 10 mutasyonu olmayan gruba göre istatistiksel olarak daha yüksekti (p=0,004).
Sonuç: M694V mutasyonu sadece bir alelde mevcut olsa bile, M694V ve non-ekson 10 mutasyonu olan çocuklar arasında anlamlı bir fark vardır. AAA ile aile öyküsü, kas-iskelet sistemi semptomları ve kolşisine yanıtsızlık ana parametrelerdir.

Keywords

Ailevi Akdeniz Ateşi, M694V, MEFV mutasyonu, kolşisin

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