E148Q variant: a familial Mediterranean fever-causing mutation or a sequence variant?

Area of Science:

• Genetics
• Immunology
• Autoinflammatory Diseases

Background:

• Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease caused by MEFV gene mutations.
• The pathogenic role of the p.E148Q variant in FMF remains debated, with varying prevalence across ethnic groups.

Purpose of the Study:

• To assess clinical characteristics and FMF severity in patients homozygous for the p.E148Q variant.
• To evaluate the impact of the co-occurring p.V726A variant in these patients.

Main Methods:

• Retrospective cohort study of FMF patients with p.E148Q/p.E148Q or p.E148Q/p.E148Q + p.V726A variants.
• Disease severity assessed using the Tel Hashomer Key to Severity Score.
• Analysis of electronic medical records from Carmel Medical Center, Israel.

Main Results:

• 61 FMF patients included; 72% were of Druze ethnicity.
• Most patients (65.5%) had mild FMF, 31.1% had moderate FMF; no severe cases reported.
• Colchicine treatment significantly reduced C-reactive protein (CRP) levels in all patients.

Conclusions:

• The p.E148Q variant, alone or with p.V726A, is associated with mild to moderate FMF severity, supporting its pathogenic role in specific ethnicities.
• Findings aid in understanding the clinical significance of the p.E148Q variant and guide colchicine treatment decisions.