Belmahi et al. (2006) described the frequencies of the MEFV mutation spectrum among 209 North African Arab patients, clinically diagnosed with FMF. The studied group included 85 Algerian patients. Exons 5 and 10 of the MEFV gene were amplified by PCR and sequenced, while the p.E148Q mutation on exon 2 was detected by PCR-RFLP using Ava I. In 34% of the cases, the disease could be confirmed by the presence of two MEFV mutations, while in 12% only one mutation could be detected. The M694I mutation was the most common in this population (80%), whereas the M694V mutation was detected in only 5% of the patients. Belmahi et al. (2006) hypothesized that the M694I mutation is an old mutation and is localized to the region populated by Arabs who were originally Berbers. Rare alleles detected included: p.M680I, p.E148Q, p.V726A, and p.A744S. Belmahi et al. (2006) tried to estimate the MEFV mutation carrier frequency rate among a control group of 113 normal individuals, including 31 Algerians. Not a single M694V mutation could be detected, arguing against a heterozygote advantage in this population [See also: Morocco, Tunisia > Belmahi et al., 2006].

Similarly, Kogan et al. (2001) investigated the carrier rate of the most common MEFV mutations among different Jewish groups. Screening for the p.E148Q, p.V726A, and p.M694V mutations was performed in 300 Ashkenazi, 101 Iraqi, and 120 Moroccan Jews, with a resulting overall carrier frequency in the three ethnic groups, respectively, of 14%, 29%, and 21%. The frequency of subjects with two MEFV mutations who did not express FMF, the so-called phenotype III, was 1 in 300 in Ashkenazi Jews and 1 in 25 in Iraqi Jews, exceeding the reported rate of overt FMF in these ethnic groups by 40- to 240-fold.

[See also: Morocco > Gershoni-Baruch et al., 2001].

Medlej-Hashim et al. (2005) undertook a study among a group of 55 Jordanian FMF patients in order to determine the frequencies of MEFV mutations. Restriction enzyme analysis was used to identify 14 MEFV mutations in the patients, followed by single strand conformation analysis. Of the patients, 29% did not have any mutation, and 71% were homozygous or compound heterozygous mutants. p.M694V was the most frequent allele in the patients with mutations (35%), followed by p.V726A (19%), p.M680I (13%), p.E148Q (6%), p.M694I (3%). Although homozygotes were found in excess in the population, once the inbred homozygotes were removed from the data, no such excess was observed. A few patients showed the rare mutations such as: p.A744S, p.T267I, and p.F479L.

Majeed et al. (2005) screened five common known MEFV mutations (p.M694V, p.V726A, p.M694I, p.M680I, and p.E148Q) in a large number of Jordanian or Palestinian patients with FMF. Over the period of four years, 482 patients with a clinical diagnosis of FMF were referred to the FMF clinic of Jordan University Hospital, where they were tested for the five previously mentioned mutations. Of these, 407 unrelated index patients were included in this study: 189 (46%) males and 218 (54%) females. A positive family history of FMF was present in 231 (57%) patients. Of the 407 unrelated patients investigated, 239 (59%) were found to have mutations and 168 were found to have none of the studied mutations. Of the 239 patients with mutations, 92 were found to be homozygous, of whom 47 were M694V/M694V and 16 were M694I/ M694I; 53 were compound heterozygous; three had complex alleles, of whom two patients were found to have M694V/V726A-E148Q and one patient was found to have V726A/V726A-E148Q; and 91 were found to have one identifiable mutation. The genetic results in both Palestinians and Jordanians were found to be similar. Of the mutations, p.M694V, p.V726A, p.M694I, p.M680I, and p.E148Q were found to be accounted for 38, 26, 14, 10, and 13%, respectively, indicating that the five MEFV mutations are well distributed in Arabs. Twelve of the patients developed the protracted febrile myalgia syndrome (PFMS) of whom five (42%) were found to be homozygous for p.M694V. Only two developed chronic renal failure, both of whom were found to be homozygous for p.M694V and were not on colchicines prophylaxis. However, 43 (11%) patients had a family history of FMF followed by chronic renal failure, none of these family members was diabetic and none was on colchicines prophylaxis; and 15 (35%) were found to be homozygous for p.M694V. These findings promoted Majeed et al. (2005) to conclude that p.M694V seems to have an association with the development of amyloidosis and the PFMS.

[See also: Lebanon > Medlej-Hashim et al., 2001 and 2004; Kuwait > Samilchuk, 2005].

In his study of single gene disorders in Kuwait, Samilchuk (2005) detected only one referral for mutation testing for FMF. This was a Jordanian family, in which two affected sibs were found to carry the homozygous p.M694V mutation.

Delague et al. (2004) compared the specificity, sensitivity, and throughput capacity of conventional fluorescent cycle sequencing, with multiplex DNA amplification and reverse hybridization technique for detection of MEFV mutations. DNA from 100 Lebanese patients diagnosed with FMV was analyzed for mutations in exons 2, 3, 5, and 10; both by DNA sequencing, as well as by using the reverse hybridization dependent FMFStripAssay for simultaneous detection of 12 MEFV mutations. A total of 15 different mutations were identified in the patients. Sequencing identified 71% of the 200 tested alleles; 97% of these were identified by the reverse hybridization method too. Three additional mutations could be identified only by sequencing. Mutations in close proximity, such as M680I(G/C) and M680I(G/A), M694V and M694I, could also be distinguished by the FMFStripAssay.

Gershoni-Baruch et al. (2001) examined 146 unrelated FMF patients of Jewish and Arab descent for five common MEFV gene mutations (p.M694V, p.M680I, p.E148Q, p.V726A, and p.M694I). The mutations accounted for 91% of FMF chromosomes. The overall carrier rates for the 4 most common FMF mutations (p.M680I, p.M694V, p.V726A, and p.E148Q) were 1:4.5 in 407 Ashkenazi Jews, 1:4.7 in 243 Moroccan Jews, 1:3.5 in 205 Iraqi Jews, and 1:4.3 in 318 Muslim Arabs. The overall frequency of low-penetrant mutations p.E148Q and p.V726A indicated that most individuals who have a genetic diagnosis of FMF remain asymptomatic.

Belmahi et al. (2006) described the frequencies of the MEFV mutation spectrum among 209 North African Arab patients, clinically diagnosed with FMF. The studied group included 87 Moroccans. In 38% of the Moroccan patients, FMF could be confirmed by the presence of two mutant alleles, while only one mutation could be detected in 10% of the patients. Unlike among the Algerian population, the most prominent mutation in this population was p.M694V (49%) followed by p.M694I (37%). Rare alleles detected in this population included p.M680I, p.E148Q, and p.M680L. Among the controls, which included 50 Moroccans, only one was found to be heterozygous for the p.M694V mutation.

[See also: Iraq > Kogan et al., 2001; Algeria, Tunisia > Belmahi et al., 2006].

Ayesh et al. (2005) sequenced 24 known FMF mutations among 511 suspected familial Mediterranean fever Palestinian patients.  Of these 511 patients, 299 had one, two or three of the known FMF mutations.  Fourteen different mutations were identified in the FMF patients.  The five most common mutations that were found were: M694V, V726A, M694I, E148Q, and M680I that account for about 90% for all detected mutations.  The majority of the patients 38% were homozygous for six mutations including the four predominant mutations with two rare mutations.  Ninety one patients were compound heterozygous for two or three mutations.  The remaining patients had only one of the 24 known mutations; these patients may express pseudo-dominancy in the related mutations or have been misdiagnosed with other FMF-like diseases.

[See also: Jordan > Majeed et al., 2005].

Mattit et al. (2006) carried out a study to identify the frequency for the five most common MEFV gene mutations in both Syrian FMF patients and the Syrian population in general and to analyze their genotype/phenotype correlations. Eighty three non-related clinically diagnosed patients with FMF and 242 non-related apparently healthy Syrian individuals were used in the study. Restriction enzyme analysis was used to detect the five most common MEFV gene mutations, followed by sequencing of exon 10 for patients' DNA where only one or no mutation was detected. Mattit et al. (2006) found that p.M694V was the most common allele (46%; 1% in controls); a result consistent with several studies in other populations. The p.V726A mutation was the second most common one (14%; 2% in controls), followed by p.M680I (10%; absent in controls), p.E148Q (6%; 7%) and p.M694I (5%; absent in controls). In addition, p.A744S (1%) and p.R761H (0.6%) mutations were detected by sequencing the entire coding region of exon 10. Both these mutations were rare and not tested in the control group in this study. In contrast with the patient's group, p.E148Q was the most common mutation among the Syrian healthy population. Mattit et al. (2006) hypothesized that the highest frequency of this mutation in the population is probably due to the reduced penetrance of this mutation and also explains the fact that a considerable proportion of genetically affected individuals remain asymptomatic. This study showed that the carrier rate in the Syrian population was high (1:5.7), prompting Mattit and colleagues (2006) to suggest that FMF is among the most prevalent familial disorder in the Syrian population. The p.M694V and, to a lesser extent, the p.M680I mutation were found to be associated with the most severe clinical features with amyloidosis.

Belmahi et al. (2006) described the frequencies of the MEFV mutation spectrum among 209 North African Arab patients, clinically diagnosed with FMF. The studied group included 37 Tunisians. The FMF could be confirmed in 19% of the patients as caused due to two detectable mutations, FMF, while only one mutation could be detected in 16% of the patients. Just like among the Moroccan population, the most prominent mutation in this population was p.M694V (10%) followed by p.M694I (5%). Belmahi et al. (2006) proposed that the p.M694V mutation arrived to the Maghreb region with migrations from the Middle East. Rare alleles detected in this population included p.M680I, p.E148Q, and p.A744S.

[See also: Algeria, Morocco > Belmahi et al., 2006].