Unique spectrum of MEFV mutations in Iranian Jewish FMF patients - Clinical and demographic significance

Y. Shinar*, I. Kuchuk, S. Menasherow, M. Kolet, M. Lidar, P. Langevitz, A. Livneh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1718-1722
Number of pages5
JournalRheumatology
Volume46
Issue number11
DOIs
StatePublished - Nov 2007

Keywords

  • B30.2 domain
  • Familial Mediterranean fever
  • G632S
  • Haplotype
  • Iranian Jew
  • Mediterranean fever gene
  • Mutation
  • PRYSPRY
  • Pyrin
  • Tertiary (3D) structure

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