Mutational analysis of the PRYSPRY domain of pyrin and implications for familial mediterranean fever (FMF)
Related Experiment Video
Updated: Aug 8, 2026
Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing
Published on: February 10, 2023
G N Goulielmos1, E Fragouli, I Aksentijevich
1Department of Internal Medicine, University of Crete, Heraklion, Greece. guolielmos@med.uoc.gr
Abstract:
Familial Mediterranean fever (FMF) is an autosomal, recessively inherited disease, characterized by recurrent fever and serositis that affects mainly patients of the Mediterranean basin. The gene responsible for FMF, named MEFV, was cloned and several missense mutations were found to be responsible for the disease. Based on a recent molecular analysis of MEFV gene mutations in 43 patients from Crete aiming to correlate specific genotypes and clinical manifestations of FMF, we were prompted to construct a three-dimensional model (3-D model) of the PRYSPRY domain of pyrin. The majority of the known MEFV mutations located on this domain have been classified, according to disease severity, and localized on this 3-D model. The functional consequences of these mutations and their implications on disease severity are discussed. Moreover, we report a putative novel missense mutation, S702C, which we identified in exon 10 of the MEFV gene and localized on the constructed 3-D model.
Insights
Familial Mediterranean Fever (FMF) is a genetic disorder affecting Mediterranean populations. This study models the MEFV gene
Area of Science:
- Genetics
- Molecular Biology
- Rheumatology
Background:
- Familial Mediterranean Fever (FMF) is an autosomal, recessively inherited autoinflammatory disorder.
- It is characterized by recurrent fever and serositis, primarily affecting individuals from the Mediterranean basin.
- The MEFV gene, encoding pyrin, is responsible for FMF, with numerous missense mutations identified.
Purpose of the Study:
- To construct a three-dimensional (3-D) model of the pyrin PRYSPRY domain.
- To correlate MEFV gene mutations with clinical manifestations of FMF.
- To investigate the functional consequences and disease severity implications of these mutations.
Main Methods:
- Molecular analysis of MEFV gene mutations in 43 patients from Crete.
- Construction of a 3-D model of the pyrin PRYSPRY domain.
- Localization and classification of known MEFV mutations on the 3-D model.
Main Results:
- The majority of known MEFV mutations within the PRYSPRY domain were classified by disease severity and mapped onto the 3-D model.
- Functional consequences and disease severity implications of these mutations were discussed.
- A putative novel missense mutation, S702C in exon 10 of the MEFV gene, was identified and localized on the 3-D model.
Conclusions:
- The 3-D model provides a structural framework for understanding MEFV mutations in FMF.
- Mutation localization and classification aid in predicting disease severity and functional impact.
- Identification of novel mutations like S702C expands the genotypic landscape of FMF.
