title: Clinical and Genetic Features of Patients With TNFRSF1A Variants in Japan: Findings of a Nationwide Survey.
abstract: To elucidate the clinical and genetic features of patients with TNFRSF1A variants in Japan using data obtained from a nationwide survey conducted by the Ministry of Health, Labor, and Welfare of Japan study group for tumor necrosis factor receptor-associated periodic syndrome (TRAPS).
  
  
  
  Inquiries were sent to 2,900 departments of internal medicine and pediatrics in all hospitals with more than 200 beds in Japan, asking whether they had patients in whom TRAPS was suspected. Genetic tests for TNFRSF1A, MEFV, and MVK were performed on 169 patients. Cell surface expression of TNFRSF1A variants was assessed using 293T cells.
  
  
  
  Ten patients from 10 independent families were found to have TNFRSF1A variants. We collected clinical and genetic information on 41 additional patients with TNFRSF1A variants and symptoms of inflammation from 23 independent families; 17 of these patients had not been described in the literature. The common clinical features of Japanese patients were fever of >38°C (100% of patients), arthralgia (59%), and rash (55%). The prevalence of abdominal pain (36%), myalgia (43%), and amyloidosis (0%) was significantly lower in Japanese patients than in Caucasian patients. The most common variant was T61I (appearing in 49% of patients), and it was identified in 7 of 363 healthy controls. Defects in cysteine residues and the T50M variant were associated with decreased cell surface expression, while other variants, including T61I, were not.
  
  
  
  Patients with TNFRSF1A variants are very rare in Japan, as in other countries, but there are a number of clinical and genetic differences between Japanese and Caucasian patients. The pathogenic significance of the T61I variant remains unclear.
authors.affiliation: Kyushu University, Fukuoka, Japan.
authors.forename: Naoyasu
authors.initials: N
authors.lastname: Ueda
authors.affiliation: Kurume University School of Medicine, Kurume, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ida
authors.affiliation: St. Mary's College, Kurume, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Washio
authors.affiliation: National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Miyahara
authors.affiliation: Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Tokunaga
authors.affiliation: National Hospital Organization Ureshino Medical Center, Ureshino, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Tanaka
authors.affiliation: Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kusuhara
authors.affiliation: Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ohmura
authors.affiliation: Kazusa DNA Research Institute, Kisarazu, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Kazusa DNA Research Institute, Kisarazu, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohara
authors.affiliation: Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Nishikomori
authors.affiliation: Jichi Medical University, Shimono, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Minota
authors.affiliation: Kagoshima University Graduate School of Health Science, Kagoshima, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Takei
authors.affiliation: Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ishigatsubo
authors.affiliation: Kyushu University, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsukamoto
authors.affiliation: Kyushu University, Fukuoka, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tahira
authors.affiliation: Kyushu University Beppu Hospital, Beppu, Japan. horiuchi@beppu.kyushu-u.ac.jp.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Horiuchi
mesh_terms: D015746:Abdominal Pain / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D018771:Arthralgia / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D005076:Exanthema / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005334:Fever / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D005434:Flow Cytometry; D057809:HEK293 Cells; D056660:Hereditary Autoinflammatory Diseases / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D008875:Middle Aged; D063806:Myalgia / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D016133:Polymerase Chain Reaction; D000071198:Pyrin / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*; D055815:Young Adult
chemical_list: C000604192:MEFV protein, human; D000071198:Pyrin; D047888:Receptors, Tumor Necrosis Factor, Type I; C506235:TNFRSF1A protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase