Genotype/phenotype correlations in Arab patients with familial Mediterranean fever

• Published in: Seminars in arthritis and rheumatism 2002-06, Vol.31 (6), p.371-376
• Main Authors: Majeed, Hasan A., El-Shanti, Hatem, Al-Khateeb, Mohammed S., Rabaiha, Z.Abu
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Arabs; Biological and medical sciences; Child; Child, Preschool; Colchicine - therapeutic use; Cytoskeletal Proteins; DNA Mutational Analysis; Familial Mediterranean Fever - ethnology; Familial Mediterranean Fever - genetics; Familial Mediterranean Fever - physiopathology; Familial Mediterranean fever gene mutations; Genotype; genotype-phenotype correlation; Humans; Infant; Jordan - ethnology; marinostrin; Medical sciences; Mutation; Phenotype; Proteins - genetics; Pyrin; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Severity of Illness Index
• ISSN: 0049-0172; 1532-866X
• DOI: 10.1053/sarh.2002.32551

Objectives: To study the phenotype/genotype correlations in Arab patients with familial Mediterranean fever (FMF). Patients and Methods: The study was performed in a 3-year period (February 1998–February 2001). Patients were seen in the pediatric FMF clinic of Jordan University Hospital, and the diagnosis of FMF was made according to published criteria. Screening for mutations was carried out by direct sequencing of the entire coding sequence of exon 10 and its donor splice site and by restriction endonuclease testing for mutations in exon 2. A total of 278 patients with clinically positive FMF were screened. Results: Of the 278 patients, 50 (18%) had 2 mutations identified, and 76 (27%) other patients had only 1 mutation identified. The 50 patients with 2 mutations are the subject of this report. The M694V/M694V and the M694V/V726A and M694I/M694I genotypes were the most common (30%, 16%, and 14%, respectively). Three homozygous genotypes (M694V/M694V, V726A/V726A, and M694I/M694I) and 2 compound heterozygous genotypes (M694V/V726A and V726A/M680I) accounted for 78% of mutations. The difference in the mean severity score (14 ± 2) of the M694V/M694V group and the V726A/V726A (mean severity score, 10 ± 3) and M694I/M6941 (mean severity score, 6 ± 1) groups was statistically significant (P =.003 and.0, respectively). The difference between the M649V/M694V group and the M694V/V726A (mean severity score, 15 ± 2) was not statistically significant (P = 0.31). Conclusions: The genotypes M694V/M694V and M694V/V726A have a severe clinical course in Arab patients with FMF, whereas the M694I/M694I is associated with mild disease. Semin Arthritis Rheum 31:371-376. Copyright 2002, Elsevier Science (USA). All rights reserved.