I591T MEFV mutation in a Spanish kindred: is it a mild mutation, a benign polymorphism, or a variant influenced by another modifier?
✍ Scribed by Anna Aldea; Jordi Casademont; Juan I. Aróstegui; Josefa Rius; Montserrat Masó; Jordi Vives; Jordi Yagüe
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 83 KB
- Volume
- 20
- Category
- Article
- ISSN
- 1059-7794
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✦ Synopsis
Communicated by Richard G.H. Cotton
Familial Mediterranean fever (FMF, MIM# 249100) is an autosomal recessive disease described mostly in the Mediterranean area and characterized by recurrent febrile episodes in association with peritonitis, pleuritis, and arthritis. In 1997, the gene responsible for FMF disease, the MEFV gene [French FMF Consortium, 1997;International FMF Consortium, 1997], was cloned. Today more than 25 MEFV mutations have been reported and those occurring in exon 10, especially at the M694 position, have a high penetrance and a severe impact on the course of the disease. In particular, the M694V mutation correlates with a higher amyloidosis risk and severe phenotype in certain populations [Cazeneuve et al., 1999]. Furthermore, the M694I severe mutation may also be amyloidogenic [Mansour et al., 2001]. Finally, the deletion of this codon in one single allele gives rise to the FMF phenotype and a true dominant transmission of the disease [Booth et al., 2000]. However, mild mutations such as E148Q, K695R, and P369S have also been described in the MEFV gene [Aksentijevich et al., 1999]. Among these, the E148Q variant may affect the patient phenotype, depending on the genetic background. It has therefore been suggested that E148Q is a functional polymorphism [Touitou, 2001].
Here, we report a Spanish kindred where the proband was the only one of three siblings to have FMF symptoms, though all three carry the I591T/ M694I genotype. The index case, a 25-year-old male, presented the first clinical symptoms of FMF at the age of 19. Recurrent attacks consisted of bouts of fever up to 391C with 24 to 48 hr of duration, occurring weekly at the beginning but monthly during the course of the disease. Fever was accompanied by abdominal pain and sinovitis, though no erisipela, pleuritis, myalgia, lymphadenopathies, or arthritis