Shinawi M, Brik R, Berant M, Kasinetz L, Gershoni-Baruch R
Department of Pediatrics, Rambam Medical Center, Haifa, Israel.
J Rheumatol. 2000 Jun;27(6):1492-5.
Familial Mediterranean fever (FMF) is an autosomal recessive disease that primarily affects non-Ashkenazi Jews, Armenians, Arabs, and Turks. The FMF (MEFV) gene responsible for the disease has been recently identified. Four missense mutations in exon 10 of the FMF gene seem to account for 86% of the DNA variations identified in patients with FMF. We conducted a phenotype/genotype correlation study in a homogenous population of Israeli-Moslem Arab patients with FMF and performed a mutational screening analysis on DNA samples from healthy individuals of this ethnic group.
Sixty-five patients clinically diagnosed as having FMF underwent molecular genetic studies using polymerase chain reaction and restriction endonuclease digestion methods to detect the presence of the 4 mutations (M694V, V726A, M680I, M694I). We then correlated the presence of each mutation with age of onset, clinical manifestations, and disease severity; patients whose allelic combination included M694V were then excluded from further statistical analysis, since the association of severe disease with the M694V allele has already been shown. In addition, we screened for FMF mutations the DNA samples from 318 healthy Moslem Arab individuals for the presence of these mutations.
Among the 65 patients who were clinically diagnosed as having FMF, 78.5% had one or 2 mutation-bearing chromosomes. The most prevalent mutation was V726A, followed by M680I, M694V, and M6941. No significant difference in phenotypic characteristics was found between the patients with the diverse mutations. The total carrier frequency for the 4 mutations was 10.4% (95% confidence interval 0.07 to 0.137).
A high FMF gene frequency was found among an Israeli-Moslem Arab population. Among the FMF patients from this ethnic group, several mutations were detected, none of which was found to correlate with a severe course of the disease.
家族性地中海热（FMF）是一种常染色体隐性疾病，主要影响非阿什肯纳兹犹太人、亚美尼亚人、阿拉伯人和土耳其人。导致该疾病的FMF（MEFV）基因最近已被确定。FMF基因第10外显子中的四个错义突变似乎占FMF患者中已确定的DNA变异的86%。我们在以色列穆斯林阿拉伯FMF患者的同质人群中进行了一项表型/基因型相关性研究，并对该族群健康个体的DNA样本进行了突变筛查分析。
65例临床诊断为FMF的患者采用聚合酶链反应和限制性内切酶消化方法进行分子遗传学研究，以检测4种突变（M694V、V726A、M680I、M694I）的存在。然后，我们将每种突变的存在与发病年龄、临床表现和疾病严重程度进行关联；由于已显示严重疾病与M694V等位基因相关，因此将等位基因组合包括M694V的患者排除在进一步的统计分析之外。此外，我们对318名健康穆斯林阿拉伯个体的DNA样本进行FMF突变筛查，以检测这些突变的存在。
在65例临床诊断为FMF的患者中，78.5%有一条或两条携带突变的染色体。最常见的突变是V726A，其次是M680I、M694V和M694I。不同突变患者的表型特征未发现显著差异。这4种突变的总携带频率为10.4%（95%置信区间0.07至0.137）。
在以色列穆斯林阿拉伯人群中发现了较高的FMF基因频率。在该族群的FMF患者中，检测到了几种突变，但未发现其中任何一种与疾病的严重病程相关。
