title: Novel mutations in TNFRSF1A in patients with typical tumor necrosis factor receptor-associated periodic syndrome and with systemic lupus erythematosus in Japanese.
abstract: Molecular defects of TNFRSF1A was investigated in members of a family presenting with typical phenotypes of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) and in patients with the autoimmune disorders, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Genomic DNA from the members of a family with typical TRAPS, as well as from 100 patients with SLE, 100 patients with RA and 100 healthy individuals, was studied for mutations in exons 2, 3 and 4 of the TNFRSF1A gene. All individuals were Japanese. Three novel missense mutations were identified in the TNFRSF1A. The C70G mutation was identified in family members with typical TRAPS, which was the second case in eastern Asian population. In addition, the T61I and R104Q mutations were each identified in 2 of the 100 SLE patients. The T61I mutation was identified in one of the 100 healthy individuals. No mutations were identified in the 100 RA patients. Functional analysis revealed that PMA-induced shedding of TNFRSF1A from PBMCs was impaired in a patient carrying T61I. A larger scale of study will clarify whether these two mutations, T61I and R104Q, are associated with chronic inflammatory disorders, such as SLE, or not.
authors.affiliation: Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan. horiuchi@intmed1.med.kyushu-u.ac.jp.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Horiuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsukamoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mitoma
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyagawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamimoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Yoshizawa
authors.forename: Mine
authors.initials: M
authors.lastname: Harada
authors.forename: Kenshi
authors.initials: K
authors.lastname: Hayashi
authors.forename: Chinami
authors.initials: C
authors.lastname: Hashimura
authors.forename: Motohiro
authors.initials: M
authors.lastname: Oribe
authors.forename: Seiichi
authors.initials: S
authors.lastname: Okamura
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001172:Arthritis, Rheumatoid / Q000235:genetics; D001483:Base Sequence; D005260:Female; D006801:Humans; D007564:Japan; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D010507:Periodicity; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I