Familial Mediterranean fever gene mutations in the inner northern region of Turkey and genotype-phenotype correlation in children.
OBJECTIVE
Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterised by recurrent episodes of fever, polyserositis and rash. The aim of this study was to determine the most common mutations and clinical features, and their relationships.


METHODS
The medical records of 78 patients were evaluated retrospectively. All of the patients had been diagnosed with FMF according to Tel Hashomer criteria between January 2005 and May 2008 in general paediatric clinics of the School of Medicine at Gaziosmanpasa University. Twelve mutations were detected in the 78 patients by polymerase chain reaction-enzyme-linked immunosorbent assay. The patients were classified into three groups according to allele status.


RESULTS
The most prominent clinical symptoms were abdominal pain (95%), fever (90%), arthritis (33%) and pleuritis (31%). Seventeen different genotypes were identified. The mutations were homozygous in 25 (32%) patients, compound heterozygous in 28 (36%) patients and heterozygous in 22 (28%) patients. No mutation was detected in three (4%) patients. The most frequent mutations were M694V (55%), M680I (16%), E148Q (10%) and P369S (4%). The mean symptom severity score was highest in the homozygous group, and high levels of C-reactive protein were also detected in this group.


CONCLUSIONS
In addition to clinical criteria, molecular studies for detecting disease-causing mutations are needed to establish the diagnosis of FMF. FMF patients who were homozygous for MEFV gene mutations had a higher symptom severity score and higher incidence of appendectomy. The broad spectrum of mutations may reflect intercultural interactions of ethnic groups in Anatolia. Nation-wide studies may help to determine the relationships among demographic, clinical and genetic features of FMF.
Department of Pediatrics, School of Medicine, Gaziosmanpasa University, Tokat, Turkey. drresul@hotmail.com
Resul
R
Yilmaz
Samet
S
Ozer
Huseyin
H
Ozyurt
Unal
U
Erkorkmaz
Semsettin
S
Sahin
D000293:Adolescent; D002097:C-Reactive Protein / Q000032:analysis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003078:Colchicine / Q000627:therapeutic use; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D010505:Familial Mediterranean Fever / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D000071198:Pyrin; D012189:Retrospective Studies; D014421:Turkey
D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin; D002097:C-Reactive Protein; D003078:Colchicine