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E148Q variant: a familial Mediterranean fever-causing mutation or a sequence variant?
Elham Orouk Awaad1,2, Lana Khoury1,2, Joeri W van Straalen3
1Department of Pediatrics, Lady Davis Carmel Medical Center, Haifa, Israel.
Abstract:
Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease, linked to mutations in the MEFV gene. The p.E148Q variant, found on exon 2, has an uncertain role in FMF, with debates on whether it is a benign polymorphism or a pathogenic mutation. This study aimed to assess the clinical characteristics and severity of FMF in patients homozygous for the p.E148Q variant and to evaluate the impact of the p.V726A variant in these patients. This retrospective cohort study analyzed data from electronic medical records at Carmel Medical Center, Israel. Patients who underwent genetic testing for FMF from November 2004 to December 2019 and had p.E148Q/p.E148Q or p.E148Q/p.E148Q + p.V726A variants were included. Disease severity was assessed using the Tel Hashomer Key to Severity Score. Statistical analyses compared clinical characteristics and severity between genotype groups. The study included 61 FMF patients, with 24 (39%) having p.E148Q/p.E148Q and 37 (61%) having p.E148Q/p.E148Q + p.V726A variants. The majority (72%) were Druze. Most patients (65.5%) exhibited mild disease, while 31.1% had moderate disease, with no cases of severe disease. Colchicine treatment significantly reduced CRP levels in all patients.
Conclusion:
These findings suggest that the p.E148Q variant, whether alone or with p.V726A, generally results in mild to moderate FMF severity, supporting its pathogenic role in particular ethnicity. These results contribute to understanding the clinical significance of the p.E148Q variant and considering the patient's need for Colchicine treatment.
What Is Known:
• The role of the p.E148Q variant in FMF is debated, with questions about whether it is a benign polymorphism or a pathogenic mutation. • The prevalence of MEFV variants can vary significantly among different ethnic groups.
What Is New:
• The p.E148Q variant has clinical significance in particular ethnicities, as supported by a significant reduction in CRP levels following colchicine treatment. • The p.E148Q variant, whether alone or with p.V726A, generally results in mild to moderate FMF severity.
Insights
The p.E148Q variant in Familial Mediterranean Fever (FMF) is linked to mild to moderate disease severity, particularly in specific ethnicities. Colchicine treatment effectively reduced CRP levels in patients with this FMF 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.
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