Diagnosis of familial Mediterranean fever by a molecular genetics method

Background: Familial Mediterranean fever is a recessively inherited disorder characterized by episodes of fever with abdominal pain, pleurisy, or arthritis. The familial Mediterranean fever gene, designated MEFV, was recently cloned, and at least three missense mutations (M680I, M694V, and V726A) that account for a large percentage of patients with this disease were identified. Objective: To establish a diagnostic test for familial Mediterranean fever. Design: Cross-sectional study of a convenience sample of patients attending familial Mediterranean fever clinics. Setting: Tertiary referral hospitals. Patients: 107 patients with familiar Mediterranean fever, their family members, and controls. Measurements: Mutations in the 107 samples were assessed by amplifying genomic DNA with use of primers that selectively amplify the normal or altered DNA sequence of the 3 MEFV mutations (amplification refractory mutation system [ARMS]). Mutations were independently assessed by automated sequencing of genomic DNA amplified by polymerase chain reaction to evaluate the sensitivity and specificity of the ARMS assay. Results: The ARMS assay correctly identified M680I, M694V, and V726A mutations in 82 persons with mutations documented by DNA sequencing (21 homozygotes, 2 compound heterozygotes, and 59 simple heterozygotes). Of 7 persons known from family studies to be noncarriers and 18 unrelated persons who were negative for these mutations by sequencing, none had MEFV mutations according to ARMS. Conclusion: The ARMS assay is a rapid, cost-effective, and accurate method for detecting three common mutations in familial Mediterranean fever.