Unique spectrum of MEFV mutations in Iranian Jewish FMF patients—clinical and demographic significance

• Published in: Rheumatology (Oxford, England) Vol. 46; no. 11; pp. 1718 - 1722
• Main Authors: Shinar, Y., Kuchuk, I., Menasherow, S., Kolet, M., Lidar, M., Langevitz, P., Livneh, A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2007; Oxford Publishing Limited (England)
• Subjects: Adolescent; Adult; B30.2 domain; Base Sequence; Biological and medical sciences; Child; Cytoskeletal Proteins - chemistry; Cytoskeletal Proteins - genetics; Diseases of the osteoarticular system; Familial Mediterranean fever; Familial Mediterranean Fever - genetics; Female; G632S; Haplotype; Haplotypes; Humans; Inflammatory joint diseases; Iranian Jew; Jews - genetics; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; Mediterranean fever gene; Middle Aged; Mutation; Pedigree; Protein Structure, Tertiary; PRYSPRY; Pyrin; Severity of Illness Index; Tertiary (3D) structure; Iranian Jew; B30.2 domain; Mediterranean fever gene; G632S; Tertiary (3D) structure; PRYSPRY; Familial Mediterranean fever; Mutation; Haplotype; Pyrin; Human; Diseases of the osteoarticular system; Genetic disease; Inflammatory disease; Symptomatology; Familial recurrent polyseritis; Familial mediterranean fever; Hereditary periodic fever; Jew
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/kem228

Objectives. To determine the spectrum of mutations in the Mediterranean fever gene (MEFV) of Iranian Jews with familial Mediterranean fever (FMF) and to analyse their clinical manifestations. Methods. FMF patients with both parents of Iranian-Jewish (IJ) extraction or with one IJ parent (IJ–other, 10 of each) were characterized for clinical manifestations, and the B30.2 (PRYSPRY) domain of their MEFV was sequenced for mutations. Results. Only one rare mutation, R653H, and one new mutation, G632S were present in the IJ group (in 2/10 patients), whereas the new, and common mutations were present in the IJ–other patients (8/10 patients). The new mutation was traced thrice to an IJ ancestor, and although carried asymptomatically by family members, it was over-represented in the patients (3/28 unrelated IJ alleles) compared non-affected IJ subjects (1/126 alleles, P = 0.03) or with non-Jewish Iranians (0/108 alleles, P = 0.001). The mutation was associated with a distinct phenotype regarding sites involved in the attack (P = 0.001), mild severity, sole expression of febrile episodes (P = 0.01) and a male bias (P = 0.01). In two 3D PRYSPRY models the G632S mutation was localized to a surface loop and close to a putative binding site. Conclusions. Iranian Jews with FMF have a unique spectrum of mutations including a newly described mutation with a non-typical phenotype.