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Genotype/phenotype correlations in Arab patients with familial Mediterranean fever
Hasan A Majeed1, Hatem El-Shanti, Mohammed S Al-Khateeb
1Department of Pediatrics, Faculty of Medicine, University of Jordan, Amman. pal@go.com.jo
Objectives:
To study the phenotype/genotype correlations in Arab patients with familial Mediterranean fever (FMF).
Patients And Methods:
The study was performed in a 3-year period (February 1998-February 2001). Patients were seen in the pediatric FMF clinic of Jordan University Hospital, and the diagnosis of FMF was made according to published criteria. Screening for mutations was carried out by direct sequencing of the entire coding sequence of exon 10 and its donor splice site and by restriction endonuclease testing for mutations in exon 2. A total of 278 patients with clinically positive FMF were screened.
Results:
Of the 278 patients, 50 (18%) had 2 mutations identified, and 76 (27%) other patients had only 1 mutation identified. The 50 patients with 2 mutations are the subject of this report. The M694V/M694V and the M694V/V726A and M694I/M694I genotypes were the most common (30%, 16%, and 14%, respectively). Three homozygous genotypes (M694V/M694V, V726A/V726A, and M694I/M694I) and 2 compound heterozygous genotypes (M694V/V726A and V726A/M680I) accounted for 78% of mutations. The difference in the mean severity score (14 +/- 2) of the M694V/M694V group and the V726A/V726A (mean severity score, 10 +/- 3) and M694I/M6941 (mean severity score, 6 +/- 1) groups was statistically significant (P =.003 and.0, respectively). The difference between the M649V/M694V group and the M694V/V726A (mean severity score, 15 +/- 2) was not statistically significant (P = 0.31).
Conclusions:
The genotypes M694V/M694V and M694V/V726A have a severe clinical course in Arab patients with FMF, whereas the M694I/M694I is associated with mild disease.
Insights
Familial Mediterranean Fever (FMF) genotype correlations in Arab patients reveal that M694V/M694V and M694V/V726A genotypes are linked to severe disease. Conversely, the M694I/M694I genotype is associated with a milder clinical course in FMF patients.
Area of Science:
- Genetics
- Clinical Medicine
- Molecular Biology
Background:
- Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disorder.
- Understanding genotype-phenotype correlations is crucial for predicting disease severity and guiding treatment.
- Arab populations exhibit unique genetic profiles for FMF.
Purpose of the Study:
- To investigate the relationship between specific gene mutations and clinical presentation in Arab patients diagnosed with FMF.
- To identify common FMF genotypes and their association with disease severity scores.
Main Methods:
- A cohort of 278 Arab patients with clinically diagnosed FMF was studied over three years.
- Genetic screening involved direct sequencing of exon 10 and restriction endonuclease testing for exon 2 mutations.
- Patients were categorized based on the presence of one or two identified mutations.
Main Results:
- Among 278 patients, 50 (18%) had two FMF mutations and 76 (27%) had one.
- The most prevalent genotypes were M694V/M694V (30%), M694V/V726A (16%), and M694I/M694I (14%).
- Homozygous M694V/M694V and compound heterozygous M694V/V726A genotypes showed significantly higher mean severity scores compared to M694I/M694I.
Conclusions:
- The M694V/M694V and M694V/V726A genotypes are associated with a severe clinical course in Arab FMF patients.
- The M694I/M694I genotype correlates with a milder phenotype in this population.
- These findings highlight the importance of specific genotype identification for personalized FMF management.