title: A novel mutation in the third extracellular domain of the tumor necrosis factor receptor 1 in a Finnish family with autosomal-dominant recurrent fever.
abstract: OBJECTIVE
  To investigate the presence of TRAPS (tumor necrosis factor receptor-associated periodic syndrome), which is a recently defined, dominantly inherited autoinflammatory syndrome caused by mutations in the tumor necrosis factor receptor superfamily 1A gene (TNFRSF1A, CD120a), in a Finnish family with recurrent fever.
  
  
  METHODS
  The TNFRSF1A gene was sequenced in both affected and unaffected family members. Flow cytometry and enzyme-linked immunosorbent assay analyses were used to assess membrane expression and serum levels of the TNFRSF1A protein, respectively.
  
  
  RESULTS
  A missense mutation in exon 4, located in the third extracellular domain of TNFRSF1A and resulting in an amino acid substitution (F112I) close to a conserved cysteine, was found in all 4 affected family members and in 1 asymptomatic individual. The mutation was clearly associated with low levels of soluble TNFRSF1A as well as with the clinical symptoms of recurrent fever and abdominal pain. Impaired shedding of TNFRSF1A after phorbol myristate acetate stimulation was detected in blood granulocytes and monocytes from the 3 adult family members with the mutation, but in the child bearing the mutation and showing clinical symptoms of recent onset, the shedding defect was less marked.
  
  
  CONCLUSIONS
  TRAPS should be suspected in any patient who presents with a history of intermittent fever accompanied by unexplained abdominal pain, arthritis, or skin rash, particularly in the presence of a family history of such symptoms. Screening for low serum levels of soluble TNFRSF1A identifies individuals who are likely to have TNFRSF1A mutations.
authors.affiliation: Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Nevala
authors.forename: Leena
authors.initials: L
authors.lastname: Karenko
authors.forename: Susanna
authors.initials: S
authors.lastname: Stjernberg
authors.forename: Maria
authors.initials: M
authors.lastname: Raatikainen
authors.forename: Hanna
authors.initials: H
authors.lastname: Suomalainen
authors.forename: Anssi
authors.initials: A
authors.lastname: Lagerstedt
authors.forename: Jenita
authors.initials: J
authors.lastname: Rauta
authors.forename: Michael F
authors.initials: MF
authors.lastname: McDermott
authors.forename: Pärt
authors.initials: P
authors.lastname: Peterson
authors.forename: Tom
authors.initials: T
authors.lastname: Pettersson
authors.forename: Annamari
authors.initials: A
authors.lastname: Ranki
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D005110:Extracellular Space / Q000737:chemistry; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005192:Family Health; D005260:Female; D005387:Finland; D005434:Flow Cytometry; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D017434:Protein Structure, Tertiary; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I; D012008:Recurrence
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I