MEFV mutation analysis in patients suffering from amyloidosis of familial Mediterranean fever
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Published on: June 9, 2018
A Livneh1, P Langevitz, Y Shinar
1Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer, Israel.
Abstract:
Familial Mediterranean fever (FMF) is a major cause of AA amyloidosis. Recently, the gene (MEFV) causing this disease was cloned and 16 disease associated mutations have been described. We have analyzed 178 FMF patients, 30 of whom also suffered from amyloidosis, for 4 mutations in MEFV. Mutations were identified in 29 of the FMF amyloidosis patients. 27 FMF amyloidosis patients were homozygous for M694V. One patient was found to be homozygous for both V726A and E148Q. In another patient E148Q and V726A were found on one allele, while V726A was found on the second allele. Amyloidosis was far more common among patients homozygous for M694V compared to patients with other mutations (P < 0.0001). In 3 patients homozygous for M694V, amyloidosis was the sole manifestation of the disease.
Insights
Familial Mediterranean fever (FMF) patients with the MEFV gene mutation M694V showed a significantly higher incidence of AA amyloidosis. This specific mutation, M694V, is strongly linked to developing amyloidosis in FMF patients.
Area of Science:
- Genetics
- Immunology
- Nephrology
Background:
- Familial Mediterranean fever (FMF) is a significant cause of AA amyloidosis.
- The MEFV gene, responsible for FMF, has had 16 disease-associated mutations identified.
Purpose of the Study:
- To investigate the association between specific MEFV gene mutations and the development of AA amyloidosis in FMF patients.
- To determine the frequency of four common MEFV mutations in FMF patients with and without amyloidosis.
Main Methods:
- Genetic analysis of 178 FMF patients, including 30 with amyloidosis.
- Screening for four specific mutations within the MEFV gene.
Main Results:
- Mutations were detected in 29 out of 30 FMF amyloidosis patients.
- Homozygosity for the M694V mutation was significantly more prevalent in patients with amyloidosis (P < 0.0001).
- Amyloidosis occurred as the only FMF manifestation in three patients homozygous for M694V.
Conclusions:
- The M694V mutation in the MEFV gene is strongly associated with AA amyloidosis in FMF patients.
- Homozygosity for M694V represents a significant risk factor for developing amyloidosis.
- Genetic screening for MEFV mutations, particularly M694V, is crucial for predicting and managing amyloidosis risk in FMF.
