title: Association of clinical and genetical features in FMF with focus on MEFV strip assay sensitivity in 452 children from western Anatolia, Turkey.
abstract: The aim of this study was to determine the relationship between clinical findings and the most common mutated alleles of MEFV gene in a childhood population and to determine the sensitivity of the 12-mutation-strip assay test in familial Mediterranean fever (FMF). Records of 452 FMF children living in western Anatolia, Turkey, (12.3 ± 4.7 years mean) were retrospectively reviewed. Of the 408 patients who met the Tel-Hashomer criteria, 364 were classified into two main groups (two-mutant/one-mutant allele) either of which had three subgroups. The two-mutant allele frequency was 51% and one-mutant allele 38%; 1% had complex-mutant alleles and 10% no mutant-alleles. The mean severity score was 8.3 ± 2.5. Most common clinical features were fever (81.9%), abdominal pain (86.3%) and myalgia (58.8%), and the least common ones: diarrhea (1.7%), protracted febrile myalgia (1.2%) and acute orchitis (1.5%). We detected 33 different genotypes of the MEFV gene: the most common mutant allele was M694V followed by symptomatic allele mutation of E148Q. Although not significantly associated with clinical findings, P369S mutation was not rare (7.5%). Phenotype-genotype correlation revealed that patients with two-allele mutations had more severe clinical presentation and high constipation rate (22.5%); 32.6% of patients with M694V/M694V had splenomegaly. Acute orchitis and protracted febrile myalgia as rare clinical findings were more common in M694V homozygotes. Comparisons of clinical findings among patients with one-mutation allele were made for the first time, but no significant association was found. Positive predictive value of strip assay screening for 12 mutations was recorded as 89%. We suggest that whole sequence analysis for supportive diagnosis of FMF should be performed for selected patients only.
authors: Department of Pediatrics, SB Tepecik Teaching Hospital, Tepecik, Izmir, Turkey.
authors: Can
authors: C
authors: Ozturk
authors: Oya
authors: O
authors: Halicioglu
authors: Işil
authors: I
authors: Coker
authors: Nesrin
authors: N
authors: Gulez
authors: Sumer
authors: S
authors: Sutçuoglu
authors: Neslihan
authors: N
authors: Karaca
authors: Guzide
authors: G
authors: Aksu
authors: Necil
authors: N
authors: Kutukculer
mesh_terms: D015746:Abdominal Pain / Q000175:diagnosis / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D010505:Familial Mediterranean Fever / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005334:Fever / Q000175:diagnosis / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D018908:Muscle Weakness / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D011237:Predictive Value of Tests; D000071198:Pyrin; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014421:Turkey
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin