Maruša Debeljak1, Nataša Toplak2, Nora Abazi3, Beatrix Szabados4, Velma Mulaosmanović5, Jelena Radović6, Daša Perko7, Jelena Vojnović6, Tamas Constantin4, Dafina Kuzmanovska3, Tadej Avčin8. 1. Unit for Special Laboratory Diagnostics, University Children's Hospital, University Medical Center, Ljubljana, Slovenia. 2. Department of Allergology, Rheumatology and Clinical Immunology, University Children's Hospital, University Medical Center; and Faculty of Medicine, University of Ljubljana, Slovenia. 3. University Children Hospital, Medical Faculty, Ss. Cyril and Methodius University, Skopje, Republic of Macedonia. 4. Unit of Paediatric Rheumatology, Department of Pediatrics, Semmelweis University, Budapest, Hungary. 5. Children's Hospital University, Clinical Center, Sarajevo, Bosnia and Herzegovina. 6. Faculty of Medicine, University of Niš, Serbia. 7. Department of Allergology, Rheumatology and Clinical Immunology, University Children's Hospital, University Medical Center, Ljubljana, Slovenia. 8. Department of Allergology, Rheumatology and Clinical Immunology, University Children's Hospital, University Medical Center; and Faculty of Medicine, University of Ljubljana, Slovenia. tadej.avcin@kclj.si.
Abstract
OBJECTIVES: Familial Mediterranean fever (FMF) is an autosomal-recessive disorder caused by mutations in MEFV gene. Eastern Mediterranean populations have the highest number of carriers, whereas western Mediterranean populations are less frequently affected. The aim of this study was to determine the carrier rate and spectrum of MEFV gene mutations in apparently healthy populations and in suspected FMF patients from central and southeastern European (CSEE) countries. METHODS: We screened 507 apparently healthy persons from 5 CSEE countries. Exons 2 and 10 of the MEFV gene were PCR amplified and subsequently sequenced with ABI prism310 genetic analyser. Six most common mutations in the MEFV gene were tested: V726A, K695R, M694V, M694I, M680I in exon 10, and E148Q in exon 2. In suspected FMF patients we screened all MEFV exons in selected cases. RESULTS: The overall carrier frequency of all MEFV mutations was higher than expected (9.3%). In the whole cohort we did not find any apparently healthy persons with two mutations. Heterozygous mutations were found in apparently healthy subjects from different CSEE countries as follows: Macedonia 16%, Serbia 11%, Bosnia and Herzegovina 8%, Slovenia 6% and Hungary 5%. The most common mutation in healthy controls was K695R, appearing in 40% of mutated alleles. The most common mutation in suspected FMF patients was M694V, followed by K695R. CONCLUSIONS: We found a higher than expected carrier rate of MEFV gene mutations in populations from CSEE countries. It is interesting to note that 40% of detected carriers carry the K695R mutation.
OBJECTIVES:Familial Mediterranean fever (FMF) is an autosomal-recessive disorder caused by mutations in MEFV gene. Eastern Mediterranean populations have the highest number of carriers, whereas western Mediterranean populations are less frequently affected. The aim of this study was to determine the carrier rate and spectrum of MEFV gene mutations in apparently healthy populations and in suspected FMFpatients from central and southeastern European (CSEE) countries. METHODS: We screened 507 apparently healthy persons from 5 CSEE countries. Exons 2 and 10 of the MEFV gene were PCR amplified and subsequently sequenced with ABI prism310 genetic analyser. Six most common mutations in the MEFV gene were tested: V726A, K695R, M694V, M694I, M680I in exon 10, and E148Q in exon 2. In suspected FMFpatients we screened all MEFV exons in selected cases. RESULTS: The overall carrier frequency of all MEFV mutations was higher than expected (9.3%). In the whole cohort we did not find any apparently healthy persons with two mutations. Heterozygous mutations were found in apparently healthy subjects from different CSEE countries as follows: Macedonia 16%, Serbia 11%, Bosnia and Herzegovina 8%, Slovenia 6% and Hungary 5%. The most common mutation in healthy controls was K695R, appearing in 40% of mutated alleles. The most common mutation in suspected FMFpatients was M694V, followed by K695R. CONCLUSIONS: We found a higher than expected carrier rate of MEFV gene mutations in populations from CSEE countries. It is interesting to note that 40% of detected carriers carry the K695R mutation.