Your browser does not support JavaScript!

Home    Οικογενής μεσογειακός πυρετός βιοχημική, γενετική και κλινική ανάλυση στον πληθυσμό της Κρήτης  

Results - Details

Add to Basket
[Add to Basket]
Identifier 000363855
Title Οικογενής μεσογειακός πυρετός βιοχημική, γενετική και κλινική ανάλυση στον πληθυσμό της Κρήτης
Alternative Title Familial mediterranean fever:biochemical genetic and clinical analysis in the population of crete.
Author Φραγκούλη, Ελένη Γ
Thesis advisor Γουλιέλμος, Γεώργιος
Reviewer Γαλανάκης, Εμμανουήλ
Μπούμπας, Δημήτριος
Γεωργόπουλος, Δημήτριος
Γραβάνης, Αχιλλέας
Παπαδάκη, Ελένη
Σιδηρόπουλος, Πρόδρομος
Abstract Familial Mediterranean fever (FMF) is an autosomal, recessively inherited disease, characterized by recurrent and short attacks of fever with serosal inflammation, caused by mutations in MEFV gene that encodes pyrin protein. To date more than 70 disease-associated mutations have been identified, almost all of them representing missense nucleotide changes. FMF is very common among patients with Mediterranean ancestry and although the exact prevalence is not yet known, Greeks are considered to be at “intermediate risk”. In the present study, we studied FMF patients in natives of Crete, a population sharing a common genetic and cultural background. The spectrum of MEFV gene mutations in 71 patients as well as 158 healthy controls was studied by performing a molecular analysis focused on 5 common and 7 less frequent FMF-associated mutations. We found that 59 of 71 (83.1%) FMF patients had at least one mutation, 7% were homozygotes and 49.3% heterozygotes. No mutations were detected in 12 patients (16.9%). As in high-risk populations, common MEFV mutations were found in Cretan FMF patients, with the M694V being the most penetrant and the heterozygous state being as severe as the homozygous state. E148Q and V726Α mutations were associated with mild phenotype, complex alleles were recognized in 14% and a novel mutation the S702C was identified. Population genetics analysis showed an FMF carrier frequency in healthy Cretan population of approximately 6% (1:17) and places Cretans closer to the Western rather than Eastern populations of the Mediterranean basin. Finally, we constructed a three-dimensional (3-D) model of the PRYSPRY domain of pyrin with the majority of the known mutations localized on it, and examined their implications to disease severity. According to the 3-D model showing the interaction of the PRYSPRY domain of pyrin with caspase-1, the ‘flexible loops’ of caspase-1 appear to have no access to some positions that have been associated with mild disease, suggesting that alternative pathogenic pathways leading to FMF need to be explored.
Language Greek
Subject Mediterranean fever
Μεσογειακός πυρετός
Issue date 2009-12-24
Collection   School/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
Views 300

Digital Documents
No preview available

Download document
View document
Views : 22