Related Experiment Video
Updated: Oct 4, 2025
In Vivo Modeling of the Morbid Human Genome using Danio rerio
Published on: August 24, 2013
Prediction of More Severe MEFV Gene Mutations in Childhood
Seviye Güneş-Yılmaz1, Belde Kasap-Demir2, Eren Soyaltın3
1Department of Pediatrics, University of Health Sciences, İzmir Tepecik Training and Research Hospital, İzmir, Turkey.
Aim:
This study aimed to present the demographic, clinical, and laboratory features of children clinically diagnosed with familial Mediterranean fever (FMF) and to predict more severe mutations by evaluating those findings.
Methods:
We enrolled cases diagnosed with FMF with a defined variation in at least one allele. The medical charts of the patients were reviewed retrospectively. The patients were grouped as homozygous, compound heterozygous, and simple heterozygous cases, with and without M694V mutation. We compared the data between the subgroups using logistic regression analysis and determined the risk factors for being homozygous or compound heterozygous for M694V.
Results:
A total of 263 (M/F =109/154) cases were included. The mean age at the onset of symptoms, follow-up duration, and time to diagnosis were 6.75 ± 3.9 (0.25-17) years, 51.78 ± 39.31 (6-166) months, and 9.23 ± 14.44 (1-132) months, respectively. The rates of parental consanguinity, positive family history for FMF, and FMF in a first-degree relative were 15%, 42%, and 31.4% respectively. The most common symptom was abdominal pain (85%). There was no difference between the growth parameters of the cases during the initial and final control periods. The most frequent alleles were M694V, E148Q, and V726A. The most common accompanying disease was IgA vasculitis (20%). Almost 90% of the cases fulfilled all the defined criteria. The rate of patients having a first-degree relative with FMF was higher, Hb values were lower, and the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values were higher during the attack period; the ESR and CRP values were higher in the attack-free period; and Pras disease severity scores were higher in homozygous or compound heterozygous cases carrying M694V. The presence of FMF in a first-degree relative increases the probability of being homozygous and compound heterozygous for M694V by a factor of 2.39; and each 1 unit increase in the Pras score increases this probability by a factor of 1.43. The threshold Pras score for this possibility is 5.5 (AUC = 0.651; 95% CI, 0.545-0.757; P = .006; sensitivity, 65%; specificity, 55%).
Conclusion:
M694V was the most common and severe mutation in our cohort. The presence of a first-degree relative with FMF and Pras scores ≥5.5 may predict a homozygous or compound heterozygous mutation for M694V.
Insights
Familial Mediterranean Fever (FMF) in children is often linked to the M694V mutation. A family history of FMF and a Pras score of 5.5 or higher may indicate a severe mutation.
Area of Science:
- Pediatric Rheumatology
- Genetics
- Clinical Medicine
Background:
- Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disorder.
- Characterizing FMF in children is crucial for understanding disease progression and genetic factors.
- The M694V mutation is frequently associated with FMF, but its severity and predictive factors require further investigation.
Purpose of the Study:
- To analyze the demographic, clinical, and laboratory features of children diagnosed with FMF.
- To identify clinical and genetic factors that predict more severe FMF mutations, particularly the M694V variant.
- To evaluate the correlation between specific mutations and disease presentation in a pediatric cohort.
Main Methods:
- Retrospective review of medical charts for 263 children diagnosed with FMF.
- Classification of patients based on genotype: homozygous, compound heterozygous, and simple heterozygous for FMF mutations, with a focus on M694V.
- Statistical analysis, including logistic regression, to compare subgroups and identify risk factors for homozygous/compound heterozygous M694V mutations.
Main Results:
- The M694V allele was the most frequent and associated with more severe disease.
- Children with FMF often presented with abdominal pain; IgA vasculitis was a common comorbidity.
- A family history of FMF (odds ratio 2.39) and higher Pras scores (odds ratio 1.43) predicted homozygous or compound heterozygous M694V mutations, with a threshold Pras score of 5.5.
Conclusions:
- The M694V mutation is common and linked to severe FMF in pediatric cases.
- Family history of FMF and a Pras score of 5.5 or greater are significant predictors of homozygous or compound heterozygous M694V mutations.
- These findings aid in predicting disease severity and guiding genetic counseling in pediatric FMF patients.
Related Concept Videos
01:39Mutations
01:20Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
02:41Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
02:23Master Transcription Regulators
01:18Mutations in Microorganisms
01:30Spontaneous and Induced Mutations