Familial Mediterranean Fever: Clinical and Genetic Characterization in a Mixed Pediatric Population of Jewish and Arab Patients

Brik, Riva; Shinawi, Marwan; Kepten, Ilana; Berant, Moshe; Gershoni‐Baruch, Ruth

doi:10.1542/peds.103.5.e70

Cited by 106 publications

(58 citation statements)

References 11 publications

(15 reference statements)

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“…Susceptibility to amyloidosis has been related to sex and genotypes at the MEFV and the SAA1 loci (20,30). It is higher in men, in individuals homozygous for either the M694V mutation or the complex E148Q-V726A allele (8)(9)(10)(11)(12)(13)(14)30), and in individuals homozygous for the SAA1␣ isoform (20). Polymorphisms at the MICA (major histocompatibility complex class I chain-related gene A) gene were also found to play a role as modifiers in FMF (31).…”

Section: Discussionmentioning

confidence: 98%

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The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever

Gershoni‐Baruch

Brik

Zacks

et al. 2003

Arthritis & Rheumatism

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165

103

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Objective. The clinical profile in familial Mediterranean fever (FMF), including its major manifestation, amyloidosis, is influenced by MEFV allelic heterogeneity and other genetic and/or environmental factors. In this study, we analyzed the contribution of genotypes at the MEFV and SAA1 loci to disease severity and to the development of amyloidosis, and further defined the factors affecting the clinical profile of FMF.Methods. We investigated a sample of 277 FMF patients (154 men and 123 women), including 62 patients with nephropathic amyloidosis, in whom both FMF alleles had been identified. A detailed chart review, interview, and physical examination were undertaken to determine the patients' demographic characteristics, medical history, clinical manifestations, and treatment. The disease severity score was calculated from the Tel-Hashomer key. Genotypes at the SAA1 locus (isoforms ␣, ␤, and ␥) were determined in all patients. The SAA1 13C/T polymorphism of the SAA1 promotor was analyzed in a subset of cases.Results

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Section: Discussionmentioning

confidence: 98%

“…The phenotypic variability of the disease is partly due to allelic heterogeneity. Mutation M694V and the complex V726A-E148Q allele are associated with a severe phenotype and amyloidosis (8)(9)(10)(11)(12)(13)(14). Mutation M680I is associated with a moderate form of disease (7,14).…”

mentioning

confidence: 99%

The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever

Gershoni‐Baruch

Brik

Zacks

et al. 2003

Arthritis & Rheumatism

Self Cite

165

103

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“…Mutation M694V and the complex V726A-E148Q allele (V726A associated in cis with mutation E148Q) are associated with a severe phenotype and amyloidosis. [23][24][25][26][27][28] Mutation M680I and V726A are associated with a moderate form of disease. 28 Mutation E148Q, the most common variant found in our population, with an allele frequency of up to 10%, has reduced penetrance, and many individuals, homozygotes or compound heterozygotes for these mutations, remain symptom free.…”

Section: Introductionmentioning

confidence: 99%

Prevalence and significance of mutations in the familial Mediterranean fever gene in patients with Crohn's disease

et al. 2004

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The concurrence of Crohn's disease (CD) and familial Mediterranean fever was repeatedly reported. In this study we determined the distribution and contribution of MEFV gene mutations to CD susceptibility and clinical heterogeneity. An Israeli cohort of 209 CD patients (120 men and 89 women) was investigated for mutations in the MEFV gene. A detailed chart review, interview and physical examination were used to determine sociodemographic and clinical characteristics. MEFV and NOD2/ CARD15 genotypes were analyzed in all patients and a genotype-phenotype correlation analysis was undertaken. The results of this study do not implicate MEFV mutations as major modifiers in CD. However, the E148Q MEFV variant was associated with susceptibility to perianal disease. More specifically, 19% (9/47) of CD patients with perianal disease carried the E148Q mutation compared to 6.7% (11/162) of CD patients without perianal involvement (OR 3.26, 95% CI 1.2-8.8, P ¼ 0.02). Although, for all mutations taken together, the prevalence of MEFV gene mutations among CD patients and controls was similar, the hypothesis that E148Q mutation modulates the phenotypic expression of CD is corroborated by the results of this study and needs to be further evaluated.

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“…34 This remarkable increase of M694V mutation rate in AS patients compared to healthy individuals is associated with the fact that M694V mutation is seen in cases which show the highest penetration and most severe clinical course compared to other mutations. [38][39][40][41] M694V mutation has been shown to be associated with early onset, episode frequency, arthritis, erysipelas-like erythema, and poor prognosis. 34 On the other hand, E148Q mutation has not been shown to be associated with low penetration or severe clinical course in FMF patients.…”

Section: Discussionmentioning

confidence: 99%

The Role of Mediterranean Fever Mutation in the Clinical Course and Pathogenesis of Ankylosing Spondylitis

et al. 2015

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Objectives:This study aims to investigate the role of Mediterranean fever (MEFV) gene mutations in the pathogenesis and clinical progression of disease in ankylosing spondylitis patients. Patients and methods:The study included 88 patients (60 males, 28 females; mean age 38.7±8.7 years; range 19 to 56 years) diagnosed with ankylosing spondylitis according to modified New York criteria. The patients were evaluated for peripheral joint and hip joint involvement and treatment characteristics. Using multiplex/polymerase chain reaction reverse hybridization method, the presence of 12 different MEFV mutations was investigated. Results: Of 29 patients, heterozygote mutation was detected in 24 (83%), mutations in both alleles were detected in three (10%), and combined heterozygote mutations were detected in two patients (7%). Three most common mutations were M694V (11.3%), E148Q (8%), and V726A (4.5%). In the group with mutations, symptoms had started earlier than in the other group, and the number of peripheral joints involved was higher. When both characteristics were compared with the characteristics of the group that did not have any gene mutations, the differences were statistically significant (p<0.001 and p=0.044, respectively). The highest correlation with the number of peripheral joints involved was determined for M694V mutation (p=0.034), while onset of symptoms at younger age was correlated with E148Q mutation (p=0.010). Conclusion: Based on the findings of this study and our clinical experience, it can be said that the clinical progression of ankylosing spondylitis patients with MEFV gene mutations is more severe, and this suggests that MEFV gene mutations may be contributive to ankylosing spondylitis pathogenesis.

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Familial Mediterranean Fever: Clinical and Genetic Characterization in a Mixed Pediatric Population of Jewish and Arab Patients

Cited by 106 publications

References 11 publications

The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever

The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever

Prevalence and significance of mutations in the familial Mediterranean fever gene in patients with Crohn's disease

The Role of Mediterranean Fever Mutation in the Clinical Course and Pathogenesis of Ankylosing Spondylitis

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