title: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a Dutch family: evidence for a TNFRSF1A mutation with reduced penetrance.
abstract: Mutations of the tumor necrosis factor receptor 1 (TNFRSF1A) gene underly susceptibility to a subset of autosomal dominant recurrent fevers (ADRFs). We report on a two-generation six-member Dutch family in which a novel R92P mutation and reduced plasma TNFRSF1A levels were found in all the children, including two who are unaffected. However, only the daughter proband and father exhibited a typical TNF-receptor associated periodic syndrome (TRAPS) phenotype. PCR-RFLP analysis revealed that the mutation was not present in 120 control chromosomes from unaffected Dutch individuals. As this R92P mutation is present in two unaffected carriers it appears to be less penetrant than previously reported TNFRSF1A mutations involving cysteine residues in the extracellular domains.
authors.affiliation: Unit of Molecular Medicine, Department of Diabetes and Metabolic Medicine, St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Aganna
authors.forename: I
authors.initials: I
authors.lastname: Aksentijevich
authors.forename: G A
authors.initials: GA
authors.lastname: Hitman
authors.forename: D L
authors.initials: DL
authors.lastname: Kastner
authors.forename: A I
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: F D
authors.initials: FD
authors.lastname: Posma
authors.forename: E J
authors.initials: EJ
authors.lastname: Zweers
authors.forename: M F
authors.initials: MF
authors.lastname: McDermott
mesh_terms: D015703:Antigens, CD / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005335:Fever of Unknown Origin / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D009426:Netherlands; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D004247:DNA