OBJECTIVE: To define the molecular basis of familial Mediterranean fever (FMF) in patients with only 1 mutation in the MEFV gene. METHODS: Genetic analysis was performed in 20 FMF patients, including full sequencing of complementary DNA (cDNA) samples and multiplex ligation-dependent probe amplification analysis. In patients with first-degree relatives with FMF, haplotype analysis was also performed. RESULTS: A second mutation was found in 2 patients. In the other 18 patients, we could not identify additional mutations, large genomic deletions, or duplications. Analysis of single-nucleotide polymorphisms along the cDNA ruled out a lack of expression of 1 of the alleles. In 2 of the 3 families in which more than 1 sibling had FMF, we showed that the affected siblings inherited a different MEFV allele from the parent who did not have the MEFV mutation. CONCLUSION: These findings are highly consistent with the existence of a clinical phenotype among some patients who are heterozygous for FMF and could explain the vertical transmission in some families. A single mutation in the MEFV gene may be much more common than was previously thought and may include up to 25% of patients who are diagnosed as having FMF.
OBJECTIVE: To define the molecular basis of familial Mediterranean fever (FMF) in patients with only 1 mutation in the MEFV gene. METHODS: Genetic analysis was performed in 20 FMFpatients, including full sequencing of complementary DNA (cDNA) samples and multiplex ligation-dependent probe amplification analysis. In patients with first-degree relatives with FMF, haplotype analysis was also performed. RESULTS: A second mutation was found in 2 patients. In the other 18 patients, we could not identify additional mutations, large genomic deletions, or duplications. Analysis of single-nucleotide polymorphisms along the cDNA ruled out a lack of expression of 1 of the alleles. In 2 of the 3 families in which more than 1 sibling had FMF, we showed that the affected siblings inherited a different MEFV allele from the parent who did not have the MEFV mutation. CONCLUSION: These findings are highly consistent with the existence of a clinical phenotype among some patients who are heterozygous for FMF and could explain the vertical transmission in some families. A single mutation in the MEFV gene may be much more common than was previously thought and may include up to 25% of patients who are diagnosed as having FMF.
Authors: Cristian Vergara; Arturo Borzutzky; Miguel A Gutierrez; Sergio Iacobelli; Eduardo Talesnik; María E Martinez; Lilith Stange; Javier Basualdo; Viviana Maluje; Renato Jimenez; Roberto Wiener; Javier Tinoco; Elena Jarpa; Juan I Aróstegui; Jordi Yagüe; Manuel Alvarez-Lobos Journal: Clin Rheumatol Date: 2012-01-28 Impact factor: 2.980
Authors: Jae Jin Chae; Young-Hun Cho; Geun-Shik Lee; Jun Cheng; P Paul Liu; Lionel Feigenbaum; Stephen I Katz; Daniel L Kastner Journal: Immunity Date: 2011-05-19 Impact factor: 31.745