THE MEFV GENE PATHOGENIC VARIANTS AND PHENOTYPE-GENOTYPE CORRELATION IN CHILDREN WITH FAMILIAL MEDITERRANEAN FEVER IN THE ÇANAKKALE POPULATION
Battal F, Silan F, Topaloğlu N, Aylanç H, Yıldırım Ş, Köksal Binnetoğlu F1, Tekin M1, Kaymaz N1, Ozdemir O,
*Corresponding Author: Assistant Professor Dr. Şule Yıldırım, Department of Pediatrics, Faculty of Medicine, Çanakkale Onsekiz Mart University, Terzioğlu Yerleşkesi Ek Bina, 17100, Çanakkale, Turkey. Tel: +90-286-2180018/2107. Fax: +90- 286-263-59-56. E-mail: sule.yildirim@comu.edu.tr
page: 23

RESULTS

The cohort was composed of 60 FMF children with mean ages of 10.48 4.83 (3-18 years), and a 28 male (46.7%) to 32 female (53.3%) ratio of 1:1.14. Various combinations and point pathogenic variants were detected in all patients. Forty-six (70.0%) were heterozygous, six (10.0%) were homozygous and 12 (20.0%) were compound pathogenic variant profiles (Table 1). The genetic analysis of the current 60 mutated FMF children revealed that p.Met694Val was the most frequent pathogenic variant, followed by p.Glu148Gln, p.Met6801le, p.Arg202Gln, p.Val726Ala, p.Pro369Ser and p.Lys695Arg (Table 2). The main clinical features of the patients were as follows: parental consanguinity was detected in eight (13.3%), appendectomy was detected in four (6.7%), abdominal pain was observed in 32 (53.3%), colchicine therapy in 48 (80%), fever in 14 (23.3%), arthritis in 14 (23.3%) and erysipelas-like erythema in three (5.0%). The detected pathogenic variants were mainly located at codons p.Met694Val, p.Glu148Gln, p.Met6801le, p.Arg202Gln, p.Val726Ala, p.Pro369Ser and p.Lys695Arg. The most common pathogenic variant was the p.Met694Val heterozygote (20.0%), followed by the p.Glu148Gln heterozygote (13.3%). The p.Met680Ile, p.Arg202Gln, p.Val726 Ala, p.Pro369Ser and p.Lys695Arg pathogenic variants were 11.7, 11.7, 6.7, 5.0 and 5.0%, respectively. Table 2 shows the pathogenic variant prevalence as a function of the clinical characteristics in the current FMF cohort. The compound pathogenic variants of p.Met680 Leu and p.Glu148Gln were frequently found in 14.3% of the fever cases. Notably, both the p.Met694Val and p.Met694Ile pathogenic variants were found in 6.3% of the abdominal pain group, and in 7.1% of the arthritis group (Table 2). Phenotype severity was evaluated according to the subsequent genotype (11) in 60 patients (Table 2). No difference was found when FMF patients carrying two mutated alleles (homozygous or compound heterozygous) were compared with those carrying only one mutated allele (heterozygous) (p >0.05). Two heterozygous pathogenic variants at codon p.Arg202Gln, one at codon p.Lys695 Arg and one compound heterozygous pathogenic variant at codons p.Met680Ile/p.Met694Ile were detected in children with evidence of an appendectomy. Two heterozygous pathogenic variants at codon p.Met694Val and one at codon p.Pro369Ser were detected in three children with erythema. Genotype results for 32 children (53.4%) with abdominal pain showed: two homozygotes for p.Met694Val, two homozygotes for p.Met680Ile and 20 heterozygotes for the p.Met694Val, p.Glu148Gln, p.Met680Ile, p.Val726Ala and p.Arg761His codons, and five compound heterozygotes for the codons p.Met680Ile/p.Met694Val, p.Met680 Leu/p.Glu148Gln, p.Val726Ala/p.Arg202Gln and p.Pro 369Ser/p.Glu148Gln (Table 2). Ten children with fever showed heterozygous pathogenic variants for p.Met694Val (three patients), p.Metl80 Ile (one patient), p.Arg202Gln (three patients), p.Pro369 Ser (two patients) and IL-28β (one patient). Four children with fever showed compound heterozygous pathogenic variants for codons p.Met680Leu/Pro, p.Glu148Gln and p.Val726Ala/p.Arg202Gln (Table 2). One compound heterozygous pathogenic variant at codons p.Met694Val/p.Met680Ile, one homozygous pathogenic variant at codon p.Met694Val and 12 heterozygous pathogenic variants at codons p.Met694Val, p.Met680Ile, p.Lys695Arg, p.Glu148Gln, p.Arg202Gln, p.Pro396Ser were detected in children with arthritis. Forty-eight FMF children (80.0%) were treated with colchicine (1-2 mg/ per day). One patient was unresponsive to the colchicine therapy (Table 1).



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