Hidaka Yukiko, Fujimoto Kyoko, Matsuo Norikazu, Koga Takuma, Kaieda Shinjiro, Yamasaki Satoshi, Nakashima Munetoshi, Migita Kiyoshi, Nakayama Manabu, Ohara Osamu, Hoshino Tomoaki, Nishikomori Ryuta, Ida Hiroaki
Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Division of Rheumatology, Kurume University Medical Center, Kurume, Japan.
Mod Rheumatol. 2021 May;31(3):704-709. doi: 10.1080/14397595.2020.1784542. Epub 2020 Jul 24.
To make an accurate diagnosis of systemic autoinflammatory diseases (SAIDs), clinical and genetic analyses were performed in patients with unexplained fever.
The clinical phenotype and genomic variants of 11 genes responsible for SAIDs were analyzed in 179 Japanese patients with unexplained fever. Genetic analysis was performed by next generation sequencing (NGS) on exons including exon-intron boundaries.
Three cases met the diagnostic criteria for SAIDs other than familial Mediterranean fever (FMF). Considering 176 patients with unexplained fever, 43 cases (24.0%) were clinically diagnosed as FMF. Gene variants were found in 53 cases (30.1%) when searching for variants in the 10 disease genes other than the gene. Among them, the most frequently-identified genes were , , , , and , which accounted for 14, 7, 17, 7, and 6 cases, respectively. These variants were less than 1% of healthy individuals or novel variants, but not regarded as pathogenic since the patients did not meet the diagnostic criteria of SAIDs caused by their identified variants clinically.
Twenty four percent of Japanese patients with unexplained fever were clinically diagnosed as FMF in this study. Low frequency but not pathogenic variants in genes other than were identified in 30.1% of the cases. It is not clear how much these gene variants contribute to the inflammatory phenotypes; therefore, further analysis would uncover their autoinflammatory phenotypes that cause fever.
为准确诊断系统性自身炎症性疾病（SAIDs），对不明原因发热患者进行了临床和基因分析。
对179例日本不明原因发热患者分析了11个与SAIDs相关基因的临床表型和基因组变异。采用二代测序（NGS）对包括外显子-内含子边界在内的外显子进行基因分析。
3例符合除家族性地中海热（FMF）以外的SAIDs诊断标准。在176例不明原因发热患者中，43例（24.0%）临床诊断为FMF。在除 基因外的10个疾病相关基因中寻找变异时，53例（30.1%）发现了基因变异。其中，最常鉴定出变异的基因分别是 、 、 、 、 ，分别有14、7、17、7和6例。这些变异在健康个体中的比例小于1%或为新变异，但由于患者临床上不符合由其鉴定出的变异所致SAIDs的诊断标准，因此不被视为致病性变异。
本研究中24%的日本不明原因发热患者临床诊断为FMF。30.1%的病例在除 基因外的其他基因中鉴定出低频但无致病性的变异。尚不清楚这些基因变异对炎症表型有多大影响；因此，进一步分析将揭示其导致发热的自身炎症表型。
