The risk of familial Mediterranean fever in MEFV heterozygotes: a statistical approach

Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder due to MEFV mutations and one of the most frequent Mediterranean genetic diseases. The observation of many heterozygous patients in whom a second mutated allele was excluded led to the proposal that heterozygosity...

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Bibliographic Details
Published in:PloS one 2013-07, Vol.8 (7), p.e68431-e68431
Main Authors: Jéru, Isabelle, Hentgen, Véronique, Cochet, Emmanuelle, Duquesnoy, Philippe, Le Borgne, Gaëlle, Grimprel, Emmanuel, Stojanovic, Katia Stankovic, Karabina, Sonia, Grateau, Gilles, Amselem, Serge
Format: Article
Language:English
Subjects:
Alleles
Arthritis
Biology
Carriers
Cytoskeletal Proteins - genetics
Disease
Disease control
Ethnic Groups - genetics
Familial Mediterranean fever
Familial Mediterranean Fever - epidemiology
Familial Mediterranean Fever - genetics
Fever
Gene Frequency
Gene mutation
Genetic aspects
Genetic counseling
Genetic counselling
Genetic Predisposition to Disease
Genetic screening
Genetics
Hereditary diseases
Heterozygote
Heterozygotes
Humans
Immunology
Inflammation
Life Sciences
Mathematics
Medical genetics
Medicine
Mutation
Pathogenicity
Pathogens
Patients
Pedigree
Periodic disease
Population (statistical)
Population genetics
Population levels
Prevalence
Pyrin
Pyrin protein
Retrospective Studies
Rheumatology
Risk
Risk factors
Siblings
Statistical methods
Statistics
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Description
Summary:Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder due to MEFV mutations and one of the most frequent Mediterranean genetic diseases. The observation of many heterozygous patients in whom a second mutated allele was excluded led to the proposal that heterozygosity could be causal. However, heterozygosity might be coincidental in many patients due to the very high rate of mutations in Mediterranean populations. To better delineate the pathogenicity of heterozygosity in order to improve genetic counselling and disease management. Complementary statistical approaches were used: estimation of FMF prevalence at population levels, genotype comparison in siblings from 63 familial forms, and genotype study in 557 patients from four Mediterranean populations. At the population level, we did not observe any contribution of heterozygosity to disease prevalence. In affected siblings of patients carrying two MEFV mutations, 92% carry two mutated alleles, whereas 4% are heterozygous with typical FMF diagnosis. We demonstrated statistically that patients are more likely to be heterozygous than healthy individuals, as shown by the higher ratio heterozygous carriers/non carriers in patients (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0068431