Familial Mediterranean fever: genotype-phenotype correlations in Japanese patients.
Familial Mediterranean fever: genotype-phenotype correlations in Japanese patients.
复制标题
DOI：
10.1097/md.0000000000000029
复制
发表时间：
2014-05
期刊：
影响因子：
1.6
通讯作者：
Yachie A
中科院分区：
文献类型：
--
作者：
Migita K;Agematsu K;Yazaki M;Nonaka F;Nakamura A;Toma T;Kishida D;Uehara R;Nakamura Y;Jiuchi Y;Masumoto J;Furukawa H;Ida H;Terai C;Nakashima Y;Kawakami A;Nakamura T;Eguchi K;Yasunami M;Yachie A
家族性地中海热（FMF）是由MEFV基因突变引起的自身炎症性疾病。在日本，既往报告过FMF患者，包括轻度或不完全形式。有几个因素被假定为有助于变量的突变率和FMF的表型变异。我们进行了目前的研究，以调查变量的临床表现和MEFV基因型分布在日本FMF患者的相关性。我们分析了311例FMF患者的人口统计学、临床和遗传学数据。临床上，我们将FMF分为2种表型：1）FMF的“典型”形式，和2）根据Tel Hashomer标准的FMF的“非典型”形式。具有典型FMF表型的患者具有较高的发热发作频率、较短的发热发作持续时间、更频繁的胸痛、腹痛、FMF家族史和MEFV外显子10突变。相反，具有非典型FMF表型的患者具有较低的发热发作频率和更频繁的非典型分布的关节炎、肌痛和MEFV外显子3突变。多因素分析表明，与典型FMF表现相关的变量是MEFV外显子10突变的存在。与携带2个或1个高突变（M694I）的患者相比，携带2个或1个低突变的患者的典型FMF表型频率降低，而非典型FMF表型的趋势相反。此外，与携带单一突变或无突变的患者相比，携带2个以上MEFV突变的患者发病更年轻，胸痛患病率更高。因此，MEFV外显子10突变与更典型的FMF表型相关。相比之下，超过一半的日本FMF患者没有MEFV外显子10突变，表现为非典型FMF表型，表明日本FMF患者倾向于通过MEFV突变的变异分为2种表型。
Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by MEditerranean FeVer gene (MEFV) mutations. In Japan, patients with FMF have been previously reported, including a mild or incomplete form. Several factors are presumed to contribute to the variable penetrance and to the phenotypic variability of FMF. We conducted the current study to investigate the correlation of variable clinical presentations and MEFV genotypic distributions in Japanese FMF patients. We analyzed demographic, clinical, and genetic data for 311 FMF patients enrolled in the study. Clinically, we classified FMF into 2 phenotypes: 1) the “typical” form of FMF, and 2) the “atypical” form of FMF according to the Tel Hashomer criteria. Patients with the typical FMF phenotype had a higher frequency of febrile episodes, a shorter duration of febrile attacks, more frequent thoracic pain, abdominal pain, a family history of FMF, and MEFV exon 10 mutations. Conversely, patients with the atypical FMF phenotype had a lower frequency of fever episodes and more frequent arthritis in atypical distribution, myalgia, and MEFV exon 3 mutations. Multivariate analysis showed that the variable associated with typical FMF presentation was the presence of MEFV exon 10 mutations. Typical FMF phenotype frequencies were decreased in patients carrying 2 or a single low-penetrance mutations compared with those carrying 2 or a single high-penetrance mutations (M694I), with an opposite trend for the atypical FMF phenotype. In addition, patients having more than 2 MEFV mutations had a younger disease onset and a higher prevalence of thoracic pain than those carrying a single or no mutations. Thus, MEFV exon 10 mutations are associated with the more typical FMF phenotype. In contrast, more than half of the Japanese FMF patients without MEFV exon 10 mutations presented with an atypical FMF phenotype, indicating that Japanese FMF patients tend to be divided into 2 phenotypes by a variation of MEFV mutations.