Clinical features and disease severity of Turkish FMF children carrying E148Q mutation

Abstract

BackgroundFamilial Mediterranean fever (FMF) is the most common hereditary monogenic autoinflammatory disease caused by mutations in the MEFV gene. It is controversial whether E148Q alteration is an insignificant variant or a disease‐causing mutation. The aim of this study was to evaluate the clinical features and disease severity of FMF patients carrying E148Q mutation.MethodsFiles of FMF patients were retrospectively evaluated. Patients with at least one E148Q mutation were included to the study. The clinical characteristics and disease severity of the patients who were carrying only E148Q mutation were compared with the patients who were compound heterozygous for E148Q and homozygous for M694V mutation.ResultsThe study group comprised 33 patients who were homozygous or heterozygous for E148Q; 34 with compound heterozygous E148Q mutations and 86 patients who had homozygous M694V mutation. Patients who had only E148Q mutation were found to have the oldest mean age of disease onset and lowest mean disease severity score. Attack frequency and colchicine doses were lower in patients with only E148Q mutation as compared with the other two groups. The frequency of clinical findings such as fever, abdominal pain, arthralgia, and arthritis among the three groups was similar.ConclusionFamilial Mediterranean fever patients with only E148Q mutation are presenting with late‐onset and milder disease course despite having similar clinical findings as compared with patients who had other mutations. Finally, we imply that E148Q is a mutation and colchicine treatment should be given.

Genotype Mutations in Egyptian Children with Familial Mediterranean Fever: Clinical Profile, and Response to Colchicine

“…Aydın et al reported that E148Q as a disease-causing mutation; they noted that patients with such mutation could present with late-onset and milder disease course and well response to colchicine as compared with patients who carry other mutations. 39 …”

Familial Mediterranean fever: Penetrance of the p.[Met694Val];[Glu148Gln] and p.[Met694Val];[=] genotypes

“…Conversely, there are studies that suggest that this variant is not benign and has at least some functional effect: There are multiple studies describing apparently typical FMF patients homozygous for p.Glu148Gln (Aydın et al, 2019;Topaloglu et al, 2005;Topaloglu et al, 2018 disease modifier of autoimmune disorders such as multiple sclerosis (Kümpfel et al, 2012), ulcerative colitis (Yıldırım et al, 2011), Crohn's disease (Karban et al, 2005), and rheumatoid arthritis (Rabinovich et al, 2005). It has also been associated with an increased risk for amyloidosis in autoimmune and in autoinflammatory disorders other than FMF (Aganna et al, 2004;Bunker & Gorevic, 2012).…”

A case report of a boy suffering from Type 1 Diabetes Mellitus and Familial Mediterranean Fever

“…Aydin et al demonstrated that E148Q mutation is associated with a milder disease course, despite patients may have similar clinical ndings and well response to colchicine therapy, when compared to patients with other mutations [23]. In our case, the patient presented recurrent fever episodes associated to abdominal, chest pain, and arthralgia and presented a good response to colchicine treatment.…”