Role of E148Q in familial Mediterranean fever with an exon 10 mutation in MEFV.
Role of E148Q in familial Mediterranean fever with an exon 10 mutation in MEFV.
复制标题
E148Q 在 MEFV 外显子 10 突变的家族性地中海热中的作用。
作者：
Miyashita K;Matsuda Y;Okajima M;Toma T;Yachie A;Wada T.
背景家族性地中海热（FMF）是由MEFV基因突变引起的常染色体隐性遗传病。外显子10的突变与典型的FMF相关。大多数日本典型FMF患者是外显子10的M694 I和外显子2的E148 Q的复合杂合子。然而，E148 Q的致病作用仍然存在争议。MethodsWe评估FMF患者及其家庭成员的症状和血清细胞因子。根据MEFV突变，他们被分为三个亚组：携带M694 I和E148 Q的个人（A组，n= 14），携带M694 I，但不携带E148 Q的个体（B组，n= 10），以及携带E148 Q但不携带M694 I的个体结果A组除1例外，其余均为典型FMF表型，而B、C组无一例出现发热或浆膜炎。与B组（499 ± 369 pg/mL）和C组（427 ± 410 pg/mL）相比，A组（2，806 ± 2，107 pg/mL）在无发热期的血清白细胞介素-18水平显著升高。三组间白细胞介素-6水平无差异。ConclusionsThese研究结果表明，E148 Q可能有助于携带MEFV杂合子M694 I突变的日本患者FMF的疾病发展，父母双方的基因检测将导致更好的咨询他们的孩子。
BackgroundFamilial Mediterranean fever (FMF) is an autosomal recessive disease caused by mutations in theMEFVgene. Mutations in exon 10 are associated with typical FMF. Most Japanese patients with typical FMF are compound heterozygotes of M694I in exon 10 and E148Q in exon 2. However, the pathogenic role of E148Q remains controversial.MethodsWe assessed symptoms and serum cytokines among patients with FMF and their family members. They were divided into three subgroups, based onMEFVmutations: individuals carrying M694I and E148Q (group A,n= 14), individuals carrying M694I, but not E148Q (group B,n= 10), and individuals carrying E148Q, but not M694I (group C,n= 11).ResultsAll but one individual in group A had typical FMF phenotypes, whereas no individual in groups B and C exhibited any episodes of fever or serositis. The serum levels of interleukin‐18 during the afebrile phase were significantly elevated in group A (2,806 ± 2,107 pg/mL), compared to those in groups B (499 ± 369 pg/mL) and C (427 ± 410 pg/mL). No difference in interleukin‐6 levels was observed among the three groups.ConclusionsThese findings indicated that E148Q may contribute to disease development of FMF in Japanese patients carrying the heterozygous M694I mutation inMEFVand that genetic testing of both parents would lead to better counseling for their children.