Two sisters with familial Mediterranean fever: lack of correlation between genotype and phenotype?
Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by attacks of fever and serositis. The most important complication of FMF is renal amyloidosis, which determines the prognosis. The gene coding the disease (MEFV) is identified on the 16th chromosome. The most common MEFV mutations are M694V, M680I, V726A and M694I located on exon 10 and E148Q located on exon 2. Unfortunately, genotype-phenotype correlation is not well established and there are unexplained ethnic differences in amyloidosis rates. We report two sisters with a common genotype (M694V/M694V) presenting with different phenotypic characteristics: one complaining of intermittent abdominal pain, arthritis and fever, while the other was suffering from intermittent pleuritis and fever during attacks. The observation of different phenotypic presentations with a common genotype in two family members shows that different phenotypes cannot be explained by particular mutations. To understand the correlation between genotypic and phenotypic FMF variants the existence of complex alleles, modifier loci, genetic heterogeneity and possible epigenetic factors should be studied extensively.
Kutlay
Sim
S
Ankara University School of Medicine, Department of Nephrology, Turkey. skutlay@hotmail.com
Sengul
Sule
S
Keven
Kenan
K
Erturk
Sehsuvar
S
Erbay
Bulent
B
D000328:Adult; D000686:Amyloidosis / Q000209:etiology / Q000235:genetics / Q000473:pathology; D001706:Biopsy; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D003937:Diagnosis, Differential; D010505:Familial Mediterranean Fever / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000235:genetics / Q000473:pathology; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D000071198:Pyrin; D035781:Siblings
D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin; D004247:DNA